New Hepatitis B-like virus family discovered: Metahepadnaviruses

The family Hepadnaviridae contains Hepatitis B viruses that are enveloped viruses with reverse-transcribed DNA genomes.

However, recently scientists reported the discovery of a new family of fish viruses, designated Metahepadnaviruses, which lack one of the four Open Reading Frames: the ORF X.
The ORF X encodes a 16.5-kd protein (HBxAg) with multiple functions, including signal transduction, transcriptional activation, DNA-repair and inhibition of protein degradation. The mechanism of this activity and the biologic function of HBxAg in the viral life-cycle remain largely unknown. However, it is well established that HBxAg is necessary for productive Hepattis B infection in vivo and may contribute to the oncogenic potential of Hepattis B viruses[1].

Otherwise these Metahepadnaviruses exhibit key characteristics of Hepatitis B viruses, including genome replication via protein-primed reverse-transcription and utilization of structurally related capsids[2].

The very first of these Metahepadnaviruses is the Tetra Metahepadnavirus (TMDV) of the Mexican tetra (Astyanax mexicanus). Collectors covet this species because it consists of distinct two subspecies: a 'normal' and a blind version.

Thousands of years ago, a population of Mexican tetras in northeastern Mexico swam (or was swept) from its hospitable river home into underwater caves and became trapped. Facing a dramatically different environment of near total darkness and hardly any food, the fish had to adapt very fast. Among other changes, these 'cavefish' swiftly (in evolutionary terms, within just a few thousand years) lost their pigmentation and their eyes. Regressive evolution is the correct term[3].

[1] Liang: Hepatitis B: The Virus and Disease in Hepatology – 2010
[2] Lauber et al: Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses in Cell Host & Microbe – 2017
[3] Protas et al: Regressive Evolution in the Mexican Cave Tetra, Astyanax mexicanus in Current Biology - 2008 

New Hepatitis B-like virus family discovered: Nackednaviruses

The family Hepadnaviridae contains Hepatitis B viruses that are enveloped viruses with reverse-transcribed DNA genomes.

However, recently scientists reported the discovery of a diversified family of fish viruses, designated Nackednaviruses, which lack the envelope protein gene, but otherwise exhibit key characteristics of Hepatitis B viruses, including genome replication via protein-primed reverse-transcription and utilization of structurally related capsids[1].
Phylogenetic reconstruction indicates that these two virus families, Hepadnaviridae and Nackednaviruses, separated more than 400 million years ago, even before the rise of tetrapods. Therefore, Hepatitis B viruses are of ancient origin, descending from non-enveloped progenitors in fishes.

Their envelope protein gene emerged de novo, leading to a major transition in viral lifestyle, followed by co-evolution with their hosts over geologic eras.

The scientists identified Hepatitis B-related viruses by homology searching in public sequence databases at the National Center for Biotechnology Information (NCBI). What they found were three new Hepatitis B-like viruses: African Cichlid Nackednavirus (ACNDV), Rockfish Nackednavirus (RNDV) and Sockeye Salmon Nackednavirus (SSNDV).

[1] Lauber et al: Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses in Cell Host & Microbe – 2017. See here.

Chimpanzees and an Anthrax variant

In 2001, while studying chimpanzees in the Taï National Park in Ivory Coast, Fabian Leendertz watched an alpha male named Leo vomit, climb up on a low branch, then topple over and die. Leendertz thought the chimps had died of the familiar form of anthrax, caused by Bacillus anthracis[1].
Five years later, Leendertz and his team showed that what killed the chimps was an unusual form of anthrax[2]. Now, scientists present evidence that the microbe causing it, Bacillus cereus biovar anthracis, plays a huge role in the ecology of the rainforest, apparently causing a large proportion of all mammalian deaths[3].

The Taï strain has acquired two plasmids, pXO1 and pXO2, possibly from Bacillus anthracis, encoding most of the genes that make anthrax such a formidable killer[4].

Leendertz and his team examined samples from bones and carcasses from at least 20 different species, collected in the forest. They detected the pathogen in 81 of 204 carcasses and 26 of 75 bones. In addition to chimps, six monkey species, duikers, mongooses and a porcupine died of the disease. It appears to be responsible for about 40% of observed wildlife deaths. The killer strain is not limited to the Taï forest. Leendertz and others have linked wildlife deaths to Bacillus cereus in other Central African countries.
[Bacillus cereus]
Animals contract Bacillus anthracis when they inhale or swallow hardy spores released into the soil by cadavers. But Bacillus cereus in Taï may have a very different ecology and epidemiology. The researchers are looking at other possible sources. One candidate is carrion flies. Leendertz’s team found traces of Bacillus cereus DNA in 17 flies. If they help spread the disease, that might explain how some monkey species that only live in trees become infected.

In humans, Bacillus cereus is responsible for foodborne illnesses, causing severe nausea, vomiting and diarrhea. Still, we mustn't forget those two plasmids, pXO1 and pXO2, it acquired in the rainforests of Ivory Coast. It's become a killer, very possibly even for humans.

[1] Leendertz et al: Anthrax kills wild chimpanzees in a tropical rainforest in Nature – 2004
[2] Leendertz et al: A New Bacillus anthracis Found in Wild Chimpanzees and a Gorilla from West and Central Africa in PloS Pathogens – 2006
[3] Hoffmann et al: Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest in Nature - 2017
[4] Köhler: Bacillus anthracis genetics and virulence gene regulation in Current Topics in Microbiology and Immunology - 2002

Hepatitis C Virus in Sharks

There lurks a species of sharks in the dark waters of the western Pacific Ocean: the graceful catshark (Proscyllium habereri). Little is known about this animal. It is an uncommon bottom-dwelling shark found on the shelves of continental and insular waters. The graceful catshark dwells on the sublittoral zone at depths of 50 to 300 meters. Even its food habits are vague to science; it probably feed on bony fishes, crustaceans and cephalopods.
[Foto: Rusty catshark. No image available for the Graceful catshark]

When Chinese scientists investigated an expanded group of potential arthropod and vertebrate host species, that have generally been ignored by other surveillance programs, they found a number of previously unknown viruses[1].

One of these viruses had many similarities with Hepatitis C Viruses. Its polypeptide aligned well with viruses in the genus Hepacivirus (27.9 to 29.3% overall identity).

The scientists named this novel hepacivirus the Wenling Shark Virus. It is named after the Chinese city of Wenling (traditional Chinese: 溫嶺市), a coastal community that has access to the East China Sea. It's also home of their university.

[1] Mang Shi et al: Divergent Viruses Discovered in Arthropods and Vertebrates Revise the Evolutionary History of the Flaviviridae and Related Viruses in Journal of Virology - 201. See here.

Hepatitis C Virus and Type 2 Diabetes

Hepatitis C Virus infection is a widespread condition that affects up to 170 million people worldwide. Liver cirrhosis and hepatocellular carcinoma are well-known complications of Hepatitis C Virus infection, but problems outside the liver develop in up to two-thirds of patients with Hepatitis C Virus[1].
The risk of type 2 diabetes (T2D) and insulin resistance appears to be increased in patients with Hepatitis C Virus as well. The elevated risk for T2D is present both in patients without liver dysfunction and in patients with chronic Hepatitis C Virus-related liver disease[2].

Up to 30% of patients with Hepatitis C Virus have insulin resistance or T2D and patients with Hepatitis C Virus are 1.5 to 3.8 times as likely to have T2D than the general population. Patients with Hepatitis C Virus who are at high risk for T2D due to non-Hepatitis C Virus-related risk factors have an 11-fold greater risk of developing T2D than individuals without Hepatitis C Virus[3]. Epidemiological data largely support the association between Hepatitis C Virus infection and T2D.

Several hypotheses have been proposed to explain how Hepatitis C Virus infection might increase the risk for T2D. According to Dr Tomer, co-author of the study, one way Hepatitis C Virus might influence the development of T2D is through promoting inflammation. “We know that inflammation is associated with T2D, and one hypothesis is that the virus causes inflammation by inducing cytokines, which are inflammatory mediators.”

Another hypothesis is that viral replication within infected cells may disturb normal insulin signaling, particularly in the liver, Dr Tomer said. He added that Hepatitis C Virus may also induce reactive oxygen species and create oxidative stress in the liver, disrupting glucose metabolism and glucose homeostasis.

Lastly, Hepatitis C Virus may not only infect liver cells, but also the pancreatic islet beta cells that secrete insulin, according to Dr Tomer. “Some studies have shown virus-like particles inside the islets,” he said. “But just seeing virus particles does not prove that Hepatitis C Virus infects islet cells. Hepatitis C Virus could be attaching to the cells and not actually infecting them. But this is a very intriguing hypothesis if indeed the virus can somehow cause direct infection of the pancreatic islets.”

[1] Desbois, Cacoub: Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review in World Journal of Gastroenterology - 2017
[2] Hammerstad et al: Diabetes and hepatitis C: a two-way association in Frontiers in Endocrinology - 2015
[3] Gastaldi et al: Current level of evidence on causal association between hepatitis C virus and type 2 diabetes: A review in Journal of Advanced Research – 2017. See here.

Hepatitis A Virus in Seals

Not so very long ago, scientists believed that primates – including humans - were the only species that were at risk for an infection with the Hepatitis A Virus. Over the last few years, it became evident that other species could also become infected with Hepatitis A Virus or a Hepatitis A-like virus.

At least 13 additional species of the genus Hepatovirus have now been identified[1]. These species infect several small mammals.
Recently, a new Hepatitis A Virus has been discovered in North American harbour seals (Phoca vitulina)[2]. The virus is related to human hepatitis A virus. The researchers tentatively named the virus phopivirus, although my suggestion would be Seal Hepatitis A Virus.

The data support a common ancestry between Seal Hepatitis A Virus and Human Hepatitis A Virus.

[1] Drexler et al: Evolutionary origins of hepatitis A virus in small mammals in PNAS – 2015
[2] Anthony et al: Discovery of a Novel Hepatovirus (Phopivirus of Seals) Related to Human Hepatitis A Virus in mBio - 2015

Hepatitis E Virus in Goats

Hepatitis E Virus in humans is a major cause of acute hepatitis worldwide, primarily transmitted by fecal-oral route. But there are other routes that pose an intrinsic risk to humans.

Zoonotic transmission of Hepatitis E Virus from Hepatitis E Virus infected pigs (uncooked or undercooked pork)[1] or cows (milk)[2] to humans or non-human primates has previously been confirmed. Yes, the Hepatitis E Virus is excreted into milk that is produced by infected cows. Drink it unpasteurised and you're likely to get infected.
The risk of Hepatitis E Virus in goats is only rarely studied. In large parts of China raw mutton and goat milk are traditionally consumed, which means there is certainly a risk of transmission of Hepatitis E virus from goats to humans. The risk of Hepatitis E Virus in goats is only rarely studied.

Now, researchers have studied stool, blood, tissues and milk of goats for Hepatitis E Virus infection investigation in Yunnan Province in China. Not surprisingly, a high prevalence of Hepatitis E Virus infection in goats was found[3]. Analysis revealed that all Hepatitis E Virus isolates from those goats belong to genotype 4 and subtype 4h, and shared a high similarity (>99.6%) with Hepatitis E Virus isolated from humans, swine and cows in the same area.

Which means that Hepatitis E Virus is circulating in at least four different species and that poses a near certainty that the virus will mutate in the foreseeable future.

[1] Meng et al: Prevalence of antibodies to the HEV in pigs from countries where HEV is common or rare in the human population in Journal of Medical Virology – 1999
[2] Huang et al: Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis in Hepatology – 2016
[3] Long et al: High prevalence of Hepatitis E virus infection in goats in Journal of Medical Virology – 2017

Hepatitis A Virus outbreaks mostly affecting men who have sex with men

Between June 2016 and mid-May 2017, an unusual increase in cases of Hepatitis A affecting mainly men who have sex with men (MSM) has been reported by low endemicity countries in the European Region, and in the Americas (Chile and the United States of America), according to a report by the World Health Organisation (WHO).
In the European Region, 15 countries (Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, and the United Kingdom) reported 1173 cases related to the three distinct multi-country Hepatitis A outbreaks as of 16 May 2017.

In Chile, 706 Hepatitis A cases were reported at national level as of 5 May 2017. In the United States, the New York City Health Department has noted an increase in Hepatitis A cases among MSM who did not report international travel.

In low endemicity settings, WHO recommends Hepatitis A vaccination for high-risk groups, such as travellers to endemic areas, MSM, people who inject drugs, and chronic liver disease patients. For MSM the main risk factor is related to sexual transmission, particularly oral-anal sexual contact. Most of the affected countries have routinely recommended Hepatitis A vaccine for MSM.

This event is of particular concern from a public health perspective because of the current limited availability of Hepatitis A vaccine worldwide. In addition, several national and international lesbian, gay, bisexual, and transgender (LGBT) pride festivals will take place between June and September 2017, including the World Pride Festival in Madrid, Spain between 23 June and 2 July 2017.

So far, no fatalities have been reported in connection with the ongoing outbreaks. It has the potential to spread further to the general population if control measures (vaccination, hygiene, food safety, and safer sex measures) are not adequately implemented.

Phosphate Fertilizer Kidney Disease

An unknown medical condition has been killing agricultural workers in northern Sri Lanka. The illness is officially described as a 'Chronic Kidney Disease of non-Traditional causes (CKDnT)'.

Patients with CKDnT do not have the commonly known risk factors for kidney disease, such as diabetes and hypertension. Which means that another etiology must be at work here. While northern Sri Lanka is 'blessed' with a hot climate, agricultural workers are not alike the sugar cane workers in Mesoamerica. Chronic dehydration does result in kidney problems and eventually to renal failure.
During the last 2600 years, farmers inhabiting dry zone of Sri Lanka were cultivating rice using irrigated water and organic fertilizer (for our English readers: fertiliser). Now, new varieties of rice cultivated by farmers require large amounts of chemical fertilizers.

Organic or natural fertilizers, such as manure, compost or paddy husk, all contained very low amounts of arsenic. Despite the fact that the import of arsenic containing pesticides is illegal, all tested pesticide brands contained arsenic[1]. There is evidence of a positive association between arsenic exposure and kidney disease mortality[2]. This special type of chronic kidney disease is a toxic nephropathy and arsenic may play a causative role along with a number of other heavy metals. Findings suggest that agrochemicals, especially phosphate fertilizers, are a major source of inorganic arsenic in CKDnT endemic areas in Sri Lanka.
Another possible culprit may be glyphosate (better known as RoundUp), the most widely used herbicide in the disease endemic area and its unique metal chelating properties. While the substance in itself is not considered very toxic to humans, it seems to have acquired the ability to destroy the renal tissues of thousands of farmers when it forms complexes with hard water or nephrotoxic metals[3]. It might even explain similar kidney disease epidemics observed in Andra Pradesh (India) and Central America.

Much more information about Chronic Kidney Diseases of non-Traditional (CKDnT) causes can be found here

[1] Jayasumana et al: Phosphate fertilizer is a main source of arsenic in areas affected with chronic kidney disease of unknown etiology in Sri Lanka in SpringerPlus - 2015
[2] Zheng et al: Arsenic and Chronic Kidney Disease: A Systematic Review in Current Environmental Health Reports – 2014
[3] Jayasumana et al: Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka? in International Journal of Environmental Research and Public Health – 2014

High Altitude Kidney Disease

The kidneys are a pair of bean-shaped organs. Each kidney is about the size of a fist. The kidneys' function are to filter the blood in order to remove waste, control the body's fluid balance and regulate the balance of electrolytes.

Loss of kidney function may be acute or chronic. The former is usually reversible, while the latter is permanent.
In high-altitude climbers, the kidneys play a crucial role in acclimatization and in mountain sickness syndromes through their roles in regulating body fluids, electrolyte and acid–base homeostasis[1]. The higher you climb, the lower the amount of oxygen available to your body. The kidneys react to that by temporarily decreasing plasma volume.

There is concern that living at high altitude may accelerate the progression of chronic kidney disease. Many areas of the kidney are marginally oxygenated even at sea levels. Researchers postulated that arterial hypoxemia (abnormally low level of oxygen in the blood) at high altitude poses a risk of faster disease progression in those with preexisting kidney disease[2].

A survey in Tibet to identify the prevalence and associated risk factors of chronic kidney disease in subjects living at altitudes above 3500 meters clearly showed a higher number of people that suffered from High Altitude Kidney Disease[3]. Which suggests that a chronic lack of oxygen causes chronic kidney diseases.

Much more information about Chronic Kidney Diseases of non-Traditional (CKDnT) causes can be found here

[1] Goldfarb-Rumyantzev, Alper: Short-term responses of the kidney to high altitude in mountain climbers in Nephrology, Dialysis, Transplantation – 2014
[2] Luks et al: Chronic kidney disease at high altitude in Journal of the American Society of Nephrology – 2008
[3] Chen et al: Prevalence and risk factors of chronic kidney disease: a population study in the Tibetan population in Nephrology, Dialysis, Transplantation – 2011

Sugar Cane Worker Kidney Disease

An unknown medical condition has been killing male agricultural workers in central America. The illness is officially described as a 'Chronic Kidney Disease of non-Traditional causes (CKDnT)' and it is responsible for 75% of deaths of young and middle-aged men in Nicaragua and El Salvador. Workers in the sugarcane industry are worst affected and the disease has been destroying families and communities since it emerged in the late 1990s. Some researchers suspect that a virus might be to blame as the fields are heavily infested with rodents[1].
Patients experience fever, nausea and vomiting, joint pain, muscle pain, headache, neck and back pain, weakness, and itchiness at the onset of acute kidney disease.

However, further research has now indicated that the epidemic of kidney disease among young Central American males may be the result of continued heat stress and volume depletion[2].

In Nicaragua and El Salvador, age-adjusted mortality rates from kidney disease are among the highest in the world. According to researchers, in these countries, the prevalence of kidney disease (defined as eGFR <60 mL/min/1.73m2).
“Most researchers believe the causes are multifactorial, and it is at least in part related to occupation, given the severe toll that kidney disease is taking on heavy manual laborers in the region,” explained Rebecca Laws, lead author on the study.

For the study, researchers followed 284 sugarcane workers in seven different jobs from one company in Nicaragua. Blood and urine samples were collected before and near the end of the six-month harvest season. Those workers who had the most labor-intensive jobs, cane cutters, had increased urinary NGAL (Neutrophil Gelatinase Associated Lipocalin) and IL-18 (Interleukin-18), both biomarkers of kidney injury.

Researchers observed a protective effect of consuming an electrolyte solution among cane cutters and seed cutters. This indicates there are ways to prevent kidney injury among laborers in high-heat settings.

Global warming might further give rise to the number of cases. Climate change has led to a significant rise of 0.8°C–0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves (extreme heat events)[3].

Much more information about Chronic Kidney Diseases of non-Traditional (CKDnT) causes can be found here.

[1] Murray et al: Mesoamerican nephropathy: a neglected tropical disease with an infectious etiology? in Microbes and Infection - 2015
[2] Laws et al: Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers in American Journal of Kidney Diseases - 2015

[3] Glaser et al: Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress Nephropathy in Clinical Journal of the American Society of Nephrology - 2016

Hepatitis E Virus in Niger

On 12 April 2017, the Niger Ministry of Health notified WHO of a Hepatitis E Virus outbreak in the Diffa region, located in the eastern part of the country. On 19 April 2017, the outbreak was officially declared by the Minister of Health.

Since 9 January 2017, an increase in cases of jaundice was noted at the Centre Mere-Enfant de Diffa ('Mother and Child Center of Diffa') among pregnant women. Initially, the cases presented with headache, vomiting, fever, conjunctivitis, pelvic pain and memory loss.

Yellow fever was initially suspected as the cause of this outbreak. However, considering a number of cases among pregnant women reporting to the Mother and Child Center in Diffa and the Hepatitis E Virus outbreak in neighbouring Chad, Hepatitis E Virus was also considered as a potential cause of signs and symptoms. Samples were collected and sent to Institut Pasteur de Dakar (IPD) for laboratory testing. Of the 29 samples tested so far, all tested negative for yellow fever and 15 tested positive for Hepatitis E by PCR.

As of 3 May 2017, a total of 282 suspected cases including 27 deaths have been reported. All reported deaths except for one death are among pregnant women (Case Fatality Rate: 9.6%). To date, five of the six districts in the Diffa region have reported cases, and 188 cases are from the Diffa and N’Guigmi districts. The Diffa region is a region affected by the Lake Chad basin crisis and there is frequent movement across the border.

Hepatitis E Virus in Camels

Hepatitis E Virus is a major cause of viral hepatitis globally. These days zoonotic Hepatitis E Virus is an important cause of chronic hepatitis in immunocompromised patients, but the danger always exists that the virus might mutate enough to target healthy people.
The rapid identification of novel Hepatitis E Virus variants and accumulating sequence information has prompted significant changes in taxonomy of the family Hepeviridae. This family now includes two genera: Orthohepevirus, which infects all mammalian and avian vertebrates, and Piscihepevirus, which infects only one species of fish, cutthroat trouts.

Within Orthohepevirus, there are four species, A-D, with widely differing host range[1]. Orthohepevirus A contains the Hepatitis E Virus variants infecting humans and its significance continues to expand with new clinical information. We now recognize eight genotypes within Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and HEV8, which were recently identified in dromedary[2] and Bactrian camels[3], respectively. HEV7 is an example of a novel genotype that was found to have significance to human health shortly after discovery.
So, what we now have are two new genotypes: HEV7 or Dromedary camel Hepatitis E Virus (shortened to DcHEV) and HEV8 or Bactrian camel Hepatitis E Virus (shortened to BcHEV). The later is capable of infecting humans (HHEV8) and that means there's another virus that has escaped our detection for quite some time. If it evolves even further, who knows what sort of damage it might do to humans.

[1] Sridhar et al: Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E Variants in International Journal of Molecular Science – 2017
[2] Woo et al: New hepatitis E virus genotype in camels, the Middle East in Emerging Infectious Diseases – 2014
[3] Woo et al: New hepatitis E virus genotype in Bactrian camels, Xinjiang, China, 2013 in Emerging Infectious Diseases – 2017

Hepatitis E Virus in Rabbits

Hepatitis E Virus in humans is a major cause of acute hepatitis in many developing countries in Asia and Africa, where it is transmitted by the fecal–oral route because of poor sanitation practices. Acute hepatitis E is also increasingly reported in industrialized countries, where the transmission is mainly zoonotic.

The initial discovery of Hepatitis E Virus transmission from domestic pigs has been followed by evidence that other mammals, such as wild boars and deer, are also potential reservoirs of Hepatitis E Virus[1][2].
Currently, there are four major genotypes Hepatitis E Virus known that infect mammals from a variety of species. Hepatitis E Virus-1 and Hepatitis E Virus-2 are restricted to humans and transmitted through contaminated water in developing countries. Hepatitis E Virus-3 and Hepatitis E Virus-4 infect humans, pigs and other mammals. The latter two are responsible for sporadic cases of Hepatitis E in developing and industrialized countries. Hepatitis E Virus-3 is distributed worldwide, whereas Hepatitis E Virus-4 largely is found in Asia. Hepatitis E Virus-3 and Hepatitis E Virus-4 infections have been linked to the consumption of raw or undercooked meats, such as pig liver sausages or game meats.

Recent studies have characterized new Hepatitis E Virus genotypes in isolates from rats in Germany, wild boars in Japan, and farmed rabbits in China[3][4][5].

The potential risk for zoonotic transmission of Hepatitis E Virus from rabbits in France is unknown. Cases of autochthonous hepatitis E are commonly reported in France, scientists investigated the prevalence of Hepatitis E Virus in farmed and wild rabbits[6].
One result of the study was that in France farmed and wild rabbits can be infected with Hepatitis E Virus. Analysis indicated that these French rabbit Hepatitis E Virus strain is a new genotype. The identification of a human Hepatitis E Virus strain that is closely related to rabbit Hepatitis E Virus strains reinforced the potential zoonotic risk for infection with this virus.

[1] Meng et al: A novel virus in swine is closely related to the human hepatitis E virus in Proceedings of the National Academy of Sciences – 1997
[2] Meng: Hepatitis E virus: animal reservoirs and zoonotic risk in Veterinary Microbiology – 2010
[3] Johne et al: Novel hepatitis E virus genotype in Norway rats, Germany in Emerging Infectious Diseases – 2010
[4] Takahashi et al: Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype in Journal of General Virology - 2011
[5] Geng et al: The serological prevalence and genetic diversity of hepatitis E virus in farmed rabbits in China in Infection, Genetics and Evolution – 2011
[6] Izopet et al: Hepatitis E Virus Strains in Rabbits and Evidence of a Closely Related Strain in Humans, France in Emerging Infectious Diseases - 2012

Hepatitis C Virus mutations 'outrun' immune systems

Unlike its viral cousins Hepatitis A and B, Hepatitis C Virus has eluded the development of a vaccine and infected more than 170 million people worldwide. Approximately 700,000 people die each year from the infection. The creation of a vaccine seems far more difficult that those of its brethren, Hepatitis A Virus and B Virus. Research has now identified a biological mechanism that appears to play a big role in helping Hepatitis C Virus evade both the natural immune system and vaccines[1].
The study found that some mutations occur outside of the viral sites that are typically targeted by antibody responses. Those mutations could also account for the difficulty of making an effective vaccine.

The research discovered that the effectiveness of the antibodies varied, with some viral strains very inhibited by the antibodies and others hardly affected at all. To find out what was causing the variation, the researchers next tapped into the genomes of the Hepatitis C Virus, but found nothing.

The researchers then expanded their search to the proteins on the surface of Hepatitis C Virus. They found that, while mutations in the binding site were not associated with resistance, other mutations in the surface proteins away from the binding site correlated with viruses that persisted despite antibody treatment.

These are the mutations the researchers believe may allow the viruses to avoid being blocked by antibodies altogether. If you think of it like a race, the antibody is trying to bind to the virus before it can enter the cell. These mutations may allow the virus to get into the cell before it even encounters the immune system.

[1] El-Diwany et al: Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1 in PloS Pathogens – 2017

Hepatitis A Virus in Himalayan Marmots

Hepatitis A virus (HAV) is a hepatotropic ('liverloving') picornavirus that causes acute liver disease worldwide.

Scientists recently reported the identification of a novel Hepatitis A Virus in Himalayan marmots (Marmota Himalayana) in south-western China. They tentatively named the virus Marmota Himalayana Hepatitis A Virus (MHHAV)[1].
The genomic and molecular characterization of Marmota Himalayana Hepatitis A Virus indicates that it is most closely related genetically to (Primate) Hepatitis A Virus. The virus is morphologically and structurally similar to (Primate) Hepatitis A Virus.

Phylogenetic analysis further indicated that Marmota Himalayana Hepatitis A Virus groups with known Hepatitis A viruses, but forms an independent branch and represents a new species in the genus Hepatovirus.

Evolutionary analysis of Marmota Himalayana Hepatitis A Virus and primate Hepatitis A viruses led to a most recent common ancestor estimate of 1,000 years ago, while the common ancestor of all Hepatitis A-related viruses including phopivirus can be traced back to some 1800 years ago.

The discovery of Marmota Himalayana Hepatitis A Virus may provide new insights into the origin and evolution of Hepatitis A viruses.

[1] Yu et al: A novel hepatovirus identified in wild woodchuck Marmota himalayana in Scientific Reports – 2016

Hepatitis and Energy Drinks

Well, that did take a bit longer than expected. Energy drinks can cause heart problems[1] and even death[2]. That much was already known. But now it appears that the consumption of four to five energy drinks daily for three weeks can already cause painful and potentially fatal hepatitis[3].
A previously healthy man went to his doctor complaining of malaise, anorexia, abdominal pain, nausea, vomiting, generalised jaundice, scleral icterus and dark urine. He was not on any prescription or over-the-counter medications, but reported drinking 4–5 energy drinks daily for 3 weeks prior to presentation.

Laboratory studies showed transaminitis (elevation of certain enzymes in the liver) and evidence of chronic Hepatitis C infection. A liver biopsy showed severe acute hepatitis with bridging necrosis and marked cholestasis (reduction or even stoppage of bile flow).

The development of acute hepatitis in this patient was likely secondary to excessive energy drink consumption. Energy drinks should be considered when patients arrive with acute hepatitis.

[1] Tofield: Energy drinks can cause heart problems in European Heart Journal – 2015
[2] Kaşıkçıoğlu E: Sports, energy drinks, and sudden cardiac death: stimulant cardiac syndrome in Anatolian Journal of Cardiology -2017
[3] Harb et al: Rare cause of acute hepatitis: a common energy drink in British Medical Journal – 201. See here.

Cancer as an infectious disease

If we think about infectious diseases (as opposed to non-communicable diseases) we probably know that these can be caused by viruses, bacteria, fungi, parasites and prions.

Cancer is not on this list. While some viruses can cause cancers in infected hosts, these cancers do not infect others. The cancer dies with the patient or the cure.

But times are changing. Transmissible cancers have been identified as spreading within two vertebrates, dogs (Canis lupus familiaris) and Tasmanian devils (Sarcophilus harrisii), and multiple independent lineages of transmissible cancer have been found in four species of bivalves[1].
[1] Canine Transmissible Venereal Tumor
The first transmissible cancer to be identified was Canine Transmissible Venereal Tumor (CTVT), a solid tumor that spreads within populations of dogs through sexual contact. The etiology of the disease was initially uncertain, but it is now known that transmission occurs through transfer and replication of the cancer cells themselves, rather than through viral modification of cells in each new host. An unexpected feature of CTVT is that it has repeatedly acquired new mitochondrial genomes from its hosts throughout its evolution. Analysis of the CTVT genome found that the cells have been spreading as a transmissible cancer lineage for 10,000–12,000 years[2]. Thus, these cells have been evolving and spreading as an asexual parasitic organism that has outlived its original canine host by more than 500 generations.

[2] Tasmanian Devil Facial Tumor Disease
The first case of Devil Facial Tumor Disease (DFTD) in a Tasmanian devil was found in 1996. DFTD is a solid facial tumor that spreads from animal to animal through physical contact when devils bite each other. It was identified as a transmissible cancer after sequencing of the genomes of DFTD[3]. The fatal disease continues to spread through the devil population and threatens them with extinction.
A recent report identified, a second, apparently completely independent, lineage of DFTD (termed DFT2) in a small number of devils[4]. The original Devil Facial Tumor Disease is now termed DFT1.
[Healthy Tasmanian Devil pup]

[3] Bivalve Transmissible Neoplasias
The finding of transmissible cancer in soft-shell clams and some evidence from disseminated neoplasia in mussels suggested that it could also be transmissible[5]. Recently, disseminated neoplasia was found in mussels (Mytilus trossulus), cockles (Cerastoderma edule) and golden carpet-shell clams (Polititapes aureus)[6].
As multiple lineages of transmissible cancers are spreading through multiple bivalve species, scientists decided to term these diseases 'bivalve transmissible neoplasias' (BTN).

[1] Metzger, Goff: A Sixth Modality of Infectious Disease: Contagious Cancer from Devils to Clams and Beyond in PloS Pathogens – 2016
[2] Murchison et al: Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage in Science – 2014
[3] Murchison et al: Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer in Cell – 2012
[4] Pye et al: A second transmissible cancer in Tasmanian devils in Proceedings of the National Academy of Sciences – 2016
[5] Carballal et al: Neoplastic diseases of marine bivalves in Journal of Invertebrate Pathololy – 2015
[6] Metzger et al: Widespread transmission of independent cancer lineages within multiple bivalve species in Nature - 2016

Hepatitis E Virus in Chad

From 1 September 2016 until 13 January 2017, a total of 693 cases including 11 deaths of acute jaundice syndrome (AJS) have been reported from Am Timan, Chad, a country in the north of Africa, situated south of Libya and east of Sudan[1].
Of the 50 patients with AJS who were hospitalized, 48 were tested for Hepatitis E using the Hepatitis E Virus Rapid Diagnostic Test (HEV RDT) and 27 (56.3%) tested positive. In total, at the end of epidemiological week 2, 2017, a total of 126 tests have been performed, of them 57 (45.2%) were positive, while 69 (54.8%) tested negative for Hepatitis E. 18 (31.6%) of the 57 patients that tested positive using the HEV RDT also had a positive malaria test, and 20 (29%) out of 69 patients that tested negative using the HEV RDT also had a positive malaria test.

Since September 2016, 11 deaths have been reported among the hospitalized cases but the total case fatality might be underestimated.

As of 13 January 2017, 16 pregnant women presenting with AJS have been hospitalized and tested for Hepatitis E, 12 (75%) of them tested positive using the HEV RDT. Of the pregnant women presenting with AJS, four have reportedly died (three had tested positive for Hepatitis E).

Approximately 90% of the AJS cases were reported from Am Timan which appears to be the epi-centre of the ongoing outbreak, and most of the cases are identified through active case findings. As of 13 January 2017, AJS cases have been reported from 59 different quartiers in and surrounding Am Timan.

[1] WHO: Disease outbreak news: Hepatitis E - Chad - January 24, 2017

Hepatitis E Virus and Guillain-Barré Syndrome

Guillain-Barré Syndrome has been abundantly in the news as a potential side-effect of an infection with the dreaded Zika virus[1], but a recent infection with the Hepatitis E Virus may be a cause of Guillain-Barré syndrome (GBS), especially in patients with elevated liver enzymes, researchers reported[2].
Of 73 patients diagnosed with GBS, retrospective study in Belgium, six (8%) tested positive on IgM assays for Hepatitis E Virus. Given the possibility of cross-reactivity with other GBS candidates like cytomegalovirus or Epstein-Barr virus, however, the researchers concluded that 4 patients in the cohort (6%) had GBS likely due to Hepatitis E Virus infection.

Along with related studies from the Netherlands and Japan, this latest study suggest that acute Hepatitis E Virus infection is associated with approximately 5% to 8% of cases of Guillain-Barre syndrome.

Classic Guillain-Barré syndrome and acute inflammatory demyelinating polyneuropathy were the most common clinical and electrophysiologic variants[3]. Neither this study nor the reports from the Netherlands and Japan observed any significant features in terms of patient age, sex, severity or duration of illness, electrophysiological findings or response to therapy (typically intravenous immunoglobulin) to differentiate between cases of GBS that were or were not associated with Hepatitis E Virus infection, the researchers said[4].

More study is needed "to better define the role of this epidemiologically important, and in many areas ubiquitous, agent in neurological diseases," the researchers wrote.

Although it is interesting to know which infection could have triggered GBS in a given patient, there are currently no therapeutic implications.

[1] Uncini et al: Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes in Journal of Neurology, Neurosurgery and Psychiatry – 2016
[2] Stevens et al: Diagnostic Challenges and Clinical Characteristics of Hepatitis E Virus–Associated Guillain-Barré Syndrome in Journal of the American Medical Association – 2016. See here.
[3] Cornblath: Electrophysiology in Guillain-Barré syndrome in Annals of Neurology - 1990 

[4] Van den Berg et al: Guillain-Barré syndrome associated with preceding hepatitis E virus infection in Neurology – 2014

Flavivirus in Soybean Cyst Nematode

Viruses of the family Flaviviridae have been well documented as the cause of major vector-borne and hepatic diseases in humans. The family currently comprises four genera: Flavivirus, Hepacivirus (Hepatitis B Viruses), Pestivirus and a newly proposed genus Pegivirus.

Viruses of the Flaviviridae have a wide host range that includes both vertebrates and invertebrates. Until recently, the only invertebrate hosts for the flaviviruses were mosquitoes and ticks, which contained viruses exclusively found within the genus Flavivirus. The remaining genera in the family—Hepacivirus, Pegivirus and Pestivirus—are exclusively found in mammals and their diversity has greatly expanded with recent virus discoveries in various mammalian species including bats, dogs, horses, pigs, ruminants and rodents.

Yet, nature always has some surprises in store.
Recently, a flavi-like virus, Soybean Cyst Nematode Virus 5 (SbCNV-5), was discovered from the soybean cyst nematode (Heterodera glycines)[1]. The soybean cyst nematode is a subterranean root pathogen that causes the most damaging disease of soybean in the US.

This novel nematode virus genome was identified in RNA sequencing data from both soybean cyst nematode eggs and second-stage juveniles. Some features of the Soybean Cyst Nematode Virus 5 had homology to pestiviruses in the family Flaviviridae.

The size of the viral genome was exceptionally long (23kb and 19kb, respectively) genomes making it larger than other known pestiviruses. Additionally, the presence of a methyltransferase in the Soybean Cyst Nematode Virus 5 genome is atypical for a pestivirus.

The scientists conclude that Soybean Cyst Nematode Virus 5 is a new flavivirus infecting soybean cyst nematodes.

[1] Bekal et al: A novel flavivirus in the soybean cyst nematode in Journal of General Virology – 2014

Hepatitis C Virus and Tattoos

When you receive a tattoo, your skin is being pierced by a needle and injected with small amounts of ink. Unsterile tattooing can transmit Hepatitis C Virus, and though it is unclear exactly what percentage of people with the virus got it through tattooing, a study found that people with Hepatitis C were almost four times more likely to report having a tattoo, even when other major risk factors were taken into account.
There is not enough research done to determine the exact percentage of people who are diagnosed with Hepatitis C and who got it through tattoos. However, a recent study discovered that people with Hepatitis C were close to four times more likely to report having a tattoo, even when other risk factors were accounted for[1].

If the tattoo was done in a prison or another non-professional setting, the risk was significantly greater[2].

For those responsible enough to go to a professional tattoo parlor where infection control measures are better, there are still health risks to consider. Most people assume that tattoo ink is ‘safe’, but the reality is that the ink is not regulated. The American FDA has received reports of bad reactions to tattoo inks right after tattooing or even years later.

Most colors of standard tattoo ink are derived from heavy metals, including lead, antimony, beryllium, chromium, cobalt nickel and arsenic.

[1] Carney et al: Association of tattooing and hepatitis C virus infection: a multicenter case-control study in Hepatology – 2013
[2] Hellard et al: Tattooing in prisons--not such a pretty picture in American Journal of Infection Control – 2007

Hepatitis viruses are leading killers

Viral hepatitis is one of the leading killers across the globe, with a death toll that matches Aids or tuberculosis, research suggests. A new report estimates that hepatitis infections and their complications led to 1.45m deaths in 2013 - despite the existence of vaccines and treatments[1]. The World Health Organization data shows there were 1.2m Aids-related deaths in 2014, while Tuberculosis led to 1.5m deaths.
Viral hepatitis usually refers to at least five different forms of virus (known as A, B, C, D and E) that can infect humans - some can be spread through contact with infected bodily fluids, while others through contaminated food or water.

Most deaths worldwide (96%) are due to Hepatitis B and C, which can cause serious liver damage (cirrhosis), and predispose people to liver cancer. But, because people don't always feel the symptoms of the initial infection, they can be unaware of the long-term damage until it is too late.

Scientists examined data from 183 countries, collected between 1990 and 2013. They found the the number of deaths linked to viral hepatitis rose by more than 60% over two decades – in part due to a growing population.

Dr Graham Cooke of Imperial College London said: "Although we have vaccines to treat Hepatitis A and B and we have new treatments for Hepatitis C, there is very little money invested in getting these to patients - especially compared to malaria, HIV/AIDS and TB.

The study suggests the problem is biggest in East Asia. But unlike many other diseases, deaths from viral hepatitis were higher in high and middle income countries than in lower income nations.

[1] Stana et al: The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013 in The Lancet – 2016

Hepatitis E Virus in Animals

Hepatitis E Virus is a major cause of enterically transmitted hepatitis worldwide. A third of the world’s population, some 2 billion people, live in areas where Hepatitis E Virus is endemic.

First a bit of a horror story: Hepatitis E was first described in 1983 when scientists reproduced Hepatitis E Virus infection in a healthy volunteer who ingested pooled stool extracts from patients presumed to have non-A, non-B hepatitis[1].

Hepatitis E Virus infection develops in most individuals as a self-limiting, acute, icteric hepatitis. Mortality rates hoover around 1%. Some affected individuals will develop hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%.
Although only a single serotype of Hepatitis E Virus has been identified, there is great genetic variation among the different Hepatitis E Virus isolates. There are at least four major recognized genotypes of Hepatitis E Virus: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in non-industrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries[2].

Thus, Hepatitis E Virus is the only one of the major Hepatitis viruses (A, B, C and D) with an animal reservoir. The discovery of Hepatitis E Virus in pigs (swine HEV), chickens (avian HEV), and, more recently, in rabbits, rodents, wild boars, ferrets, bats, sheep and cutthroat trout, as well as the successful experimental transmission of swine Hepatitis E Virus to macaques (model for human Hepatitis E Virus transmission) supports a zoonotic origin of Hepatitis E.

One possible explanation for the great genomic variability of Hepatitis E Virus is an animal origin. Analysis have shown a close relationship between swine and human isolates of the same geographic area in industrialized countries.
Rabbits have also been suggested as a zoonotic source of Hepatitis E Virus. French researchers found that farmed and wild rabbits in France are naturally infected with Hepatitis E Virus. They also characterized a human Hepatitis E Virus strain that is closely related to rabbit Hepatitis E Virus strains; this finding thus supports the potential of zoonotic transmission from rabbits to humans[3]. However, research showed that isolates from farmed, wild and pet rabbits in The Netherlands were distinct from most human isolates and are unlikely to be a zoonotic source[4].

[1] Balayan et al: Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route in Intervirology – 1983
[2] Pérez-Gracia et al: Current Knowledge on Hepatitis E in Journal of Clinical and Translational Hepatology – 2015
[3] Izopet et al: Hepatitis E Virus Strains in Rabbits and Evidence of a Closely Related Strain in Humans, France in Emerging Infectious Diseases – 2012
[4] Burt et al: Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands in Food and Environmental Virology – 2016

Geographic distribution of Hepatitis B Virus genotypes

Regarded as pandemic, Hepatitis B Virus genotype A is predominantly found in North America, Northern and Western Europe as well as Central Africa. Genotype B is most common in Asia including Japan, Taiwan, Indonesia, China and Vietnam. Genotype C is predominant in East Asia and countries of the Pacific rim while genotype D, another pandemic genotype, is most common in the Mediterranean, India, the Middle East and North America. Hepatitis B Virus genotype E is mainly detected in sub-Saharan Africa, genotype F in South and Central America as well as Alaska, and genotype G in Central and North America as well as Europe. The most recent Hepatitis B Virus genotype identified, genotype H, has been found in the United States, Mexico and Central America[1].Recently, however, a novel genotype I has been discovered.
However, although these general geographical distributions provide insight into the regional predominance of Hepatitis B Virus genotypes, the effect of travel and immigration must be kept in mind. For example, in an ongoing study involving 17 liver centres across the United States, scientists found at least seven Hepatitis B Virus genotypes in the patient population with genotypes C and A being most common followed by B and D.

It is unknown whether the global distribution of Hepatitis B Virus genotypes is related to racial or ethnic differences, modes of transmission, environmental aspects or all of these factors. Further studies are required to determine the correlation of Hepatitis B Virus genotype distribution with mode of transmission or host factors including ethnicity.

Guettouche and Hnatyszyn: Chronic hepatitis B and viral genotype: the clinical significance of determining HBV genotypes in Antiviral Therapy - 2005

Hepatitis B Virus in Amniotes

Amniotes are a clade of vertebrates comprising the reptiles, birds and mammals that lay their eggs on land or retain the fertilized egg within the mother. They are distinguished from the anamniotes (fishes and amphibians), which typically lay their eggs in water.

Recently, endogenized sequences of Hepatitis B viruses (eHBV's) have been discovered in bird and snake genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present[1].
Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals.

Recently a report was published that showed the first eHBV's from crocodilian, snake and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic 'fossil' is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepattitis B viruses already existed during the Early Mesozoic.
This implies that the Mesozoic fossil record of Hepatitis B Virus infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles.

The study reveals an unforeseen host range of prehistoric Hepatitis B viruses and provides novel insights into the genome evolution of Hepatitis B viruses throughout their long-lasting association with amniote hosts.

[1] Suh et al: Early Mesozoic Coexistence of Amniotes and Hepadnaviridae in Plos Genetics – 2016

Hepatitis B Virus in Budgerigars

Budgerigars (Melopsittacus undulatus) are better known as common pet parakeets. They are small, long-tailed, seed-eating parrots and are indigenous in the drier parts of Australia.

Screening of metazoan genome data identified multiple endogenous Hepatitis B viral elements in the budgerigar genome[1]. Phylogenetic and molecular dating analyses show that endogenous Budgerigar Hepatitis B Virus (eBHBV) share an ancestor with extant avian Hepatitis B Viruses and infiltrated the budgerigar genome millions of years ago. It could be calculated that Budgerigar Hepatitis B Virus inserted into the budgerigar genome at least 2.5 to 5.0 million years ago.
A short time later another team mined six additional avian genomes[2]. A phylogenetic analysis reveals that the endogenous Hepatitis B viruses are more diverse than their exogenous counterparts and that the endogenous and exogenous Hepatitis B viruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events.

Endogenous viral elements (EVEs) are entire or fragmented viral genomes that have been integrated into the genome of their hosts in a sometimes distant past. They are therefore vertically inherited in a stable manner[3]. These elements can be seen as the genetic ‘fossils’ of which can be detected in whole genome sequence data millions of years later.

The genomic organization of both eBHBV1 and eBHBV2 is nearly identical to that of modern-day avian Hepatitis B viruses. I suspect that endogenous Budgerigar Hepatitis B Virus will have much in common with Parrot Hepatitis B Virus as these species are closely related.

[1] Wei et al: The First Full-Length Endogenous Hepadnaviruses: Identification and Analysis in Journal of Virology - 2012
[2] Cui et al: Endogenous hepadnaviruses in the genome of the budgerigar (Melopsittacus undulatus) and the evolution of avian hepadnaviruses in Journal of Virology – 2012
[3] Holmes: The Evolution of Endogenous Viral Elements in Cell Host & Microbe – 2011

Hepatitis B Virus in Rattlesnakes

In 2014, scientific research was published that reported that it had found – among others – endogenous viral elements (EVEs) from a Hepatitis B Virus in the speckled rattlesnake (Crotalus mitchellii)[1]. Analysis reveals genome fragments from the virus family were inserted into the genome of this snake over the past 50 million years.
Endogenous viral elements (EVEs) are entire or fragmented viral genomes that have been integrated into the genome of their hosts in a sometimes distant past. They are therefore vertically inherited in a stable manner[2]. These elements can be seen as the genetic ‘fossils’ of which can be detected in whole genome sequence data millions of years later. Endogenization of viruses is not rare; in fact, it appears to be a recurrent and on-going process[3].

Further research for EVEs in the genome of the speckled rattlesnake revealed that there are two fragments with significant similarity to sequences from Hepatitis B Viruses. These were given the names endogenous Snake Hepatitis B Virus 1 and 2 (or eSHBV1 and eSHBV2).
Interestingly, the cobra and rattlesnake eSHBV1 group tightly together, as could be expected given that the two sequences are orthologous (decended from the same ancestor). EVE scans in the cobra and python genomes additionally yielded a fragment in the cobra showing 60% similarity to the core protein of the Parrot Hepatitis B Virus.

[1] Gilbert et al: Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes in Proceedings of The Royal Society – 2014
[2] Katzourakis et al: Endogenous viral elements in animal genomes in PLoS Genetics – 2010
[3] Holmes: The Evolution of Endogenous Viral Elements in Cell Host & Microbe – 2011

Hepatitis C Deaths Rising in US

Despite new curative antiviral treatments for Hepatitis C Virus infections, the number of deaths from Hepatitis C in the U.S. is on the rise, and the increase is hitting particularly hard among middle-aged people, a new study from the Centers for Disease Control and Prevention (CDC) reports[1].

The study found that the number of deaths in the U.S. from Hepatitis C rose from 11,051 in 2003 to 19,368 in 2013. And baby boomers – ages 55 to 64 – accounted for 51 percent of the deaths in 2013, according to the study. The hepatitis C virus infects the liver cells and can lead to serious liver problems, including cirrhosis (scarring of the liver) or liver cancer.
In the analysis, CDC researchers looked at data collected from death certificates in the U.S. between 2003 and 2013. The researchers compared the number of Americans who died each year from hepatitis C to the number of deaths from 60 other 'nationally notifiable' infectious conditions, such as HIV, pneumococcal disease, tuberculosis, measles, mumps, rabies and Lyme disease.

During the study period, there was an average yearly increase in deaths from hepatitis C of more than 6 percent. During the same period, deaths from the 60 other infectious conditions included in the study decreased: they fell from 24,745 in 2003 to 17,915 in 2013, or an average yearly decrease of more than 3 percent, according to the findings.

In 2012, the number of Americans who died from Hepatitis C exceeded the total number of deaths from all 60 of those other notifiable infectious conditions, the researchers found.
Hepatitis C spreads primarily when people share needles, syringes or other equipment used to inject drugs. But before 1992, when the U.S. began screening the blood supply for the virus, hepatitis C was also commonly spread through blood transfusions and organ transplants.

Many people who are currently infected with Hepatitis C are baby boomers who may have experimented once or twice with an injectable drug when they were younger. Because people are not routinely screened for Hepatitis C, about 85 percent of those infected with the virus don't even know they have it. And if you don't know you are infected, you will not get effective treatment.

[1] Holmberg et al: Continued Rising Mortality from Hepatitis C Virus in the United States, 2003-2013 in Open Forum Infectious Diseases – 2016

Hepatitis C Virus and Lactoferrin

Lactoferrin (hLF) is a multifunctional globular glycoprotein and is widely represented in the human body in various secretory fluids, such as breast milk, saliva, tears and nasal secretions.

Lactoferrin is one of the components of the immune system of the body. It has antimicrobial, antifungal and antiviral activity and is part of the innate defense, mainly at mucoses[1]. In particular, lactoferrin provides antibacterial activity to human infants. To protect the vulnerable infants against infections, human breast milk has the highest concentration of lactoferrin.
But lactoferin is not only a potent ingredient of humans, but also of other mammals, like cows. Scientists found that bovine lactoferrin (bLF) prevented Hepatitis C Virus infection in human liver cells[2]. They demonstrated that the activity of the bovine lactoferrin was due to the interaction of bovine lactoferrin and Hepatitis C Virus. It inhibited viral entry to the cells.

Further studies showed that lactoferrin even displayed activity against Influenza A Virus (H5N1)[3].

This might be a new avenue for a possible treatment for an infection with Hepatitis C Virus and maybe even all other virusses too,

[1] Sánchez et al: Biological role of lactoferrin in Archives of Diseases in Childhood – 1992
[2] Ikeda et al: Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells in Virus Research – 2000
[3] Ng et al: Antiviral activities of whey proteins in Applied Microbiology and Biotechnology – 2015

Hepatitis C Virus in Dogs

An estimated 3% of the world's population is chronically infected with Hepatitis C Virus. According to the WHO, 130–150 million people globally have a chronic Hepatitis C infection and a significant number of those who are chronically infected will develop liver cirrhosis or liver cancer. Approximately 500,000 people die each year from Hepatitis C-related liver diseases[1].

Although the Hepatitis C Virus was discovered about 25 years ago, its origin remained obscure largely because no closely related animal virus homolog had been identified before 2011.
In 2011 scientists reported the identification in domestic dogs of a nonprimate hepacivirus. Analysis of the canine hepacivirus or Canine Hepatitis C Virus confirmed it to be the most genetically similar animal virus homolog of (Human) Hepatitis C Virus[2].

Further analysis suggested a divergence time of the most recent ancestor of both viruses within the past 500-1,000 years, well after the domestication of canines. Which might mean that dogs got the virus from humans.

Non-human primates have been long suspected as harbouring viruses related to (Human) Hepatitis C Virus. A radical re-think of both the host range and host-specificity of Hepatitis C Viruses is now required following the these findings of a non-primate hepacivirus (NPHV) in horses and in dogs. Further research on a much wider range of mammals is needed to better understand the true genetic diversity of Hepatitis C-like viruses and their host ranges in the search for the ultimate origin of Hepatitis C Virus in humans[3].

[1] Lozano et al: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study in The Lancet - 2012
[2] Kapoor et al: Characterization of a canine homolog of hepatitis C virus in Proceedings of the National Academy of Sciences - 2011
[3] Simmonds: The origin of hepatitis C virus in Current Topics in Microbiology and Immunology - 2013

Evolution of Hepatitis B Virus Subtypes

Today, (Human) Hepatitis B Virus has a worldwide distribution, but it must have originated somewhere and at some point in time. Hepatitis B Virus is divided into four major serotypes (adr, adw, ayr, ayw) and into eight genotypes (A–H). Genotype A is further classified into three subgenotypes and one so-called quasi-subgenotype[1].

The majority of Hepatitis B Virus-A-subgenotypes are widespread in Africa and in ethnic groups that have relatively recently emigrated from African countries. Hepatitis B Virus-A2-subgenotype is highly prevalent among subjects at high risk for sexual exposure to Hepatitis B Virus in northwestern Europe and the USA.
Recent research found that the common ancestor of the currently circulating A-subgenotypes should be placed in west-central Africa around 1057 years ago, which means that we can put a tentative date on its origin: 958 AD[2]. This genotype diverged into two main clades at the beginning of the 13th century: one including all of the west-central African quasi-subgenotypes and the other corresponding to subgenotype A1, originating in east Africa and further segregating into two main subclades: an 'African' and a 'cosmopolitan' clade.

It is highly likely that the slave trade was the main source the spread of cosmopolitan HBV-A1, which was exported to Asia in the 17th century as a result of Arab or Portuguese trade, and to Latin America in the 18th centuries through the trans-Atlantic slave trade.

The origin of the currently circulating A2 strains dates back to the first decades of the 20th century, and the evolutionary demography analysis suggests an exponential growth of infections, between 1970s and the mid-1990s.

[1] Kramvis et al: Hepatitis B virus genotypes in Vaccine - 2005
[2] Zehender et al: Reliable timescale inference of HBV genotype A origin and phylodynamics in Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases - 2015