Hepatitis E Virus in Yellow-necked Mouse

Hepatitis E Virus is a member of the family Hepeviridae, genus Orthohepevirus. The genus includes four genotypes: Orthohepevirus A, B, C and D. Orthohepevirus A has been isolated from humans, swine (pigs and wild boars), deer, mongooses, rabbits and camels. Orthohepevirus B have been isolated from birds, Orthohepevirus C from rats, ferrets and minks. Orthohepevirus D includes strains from bats. The largest species, Orthohepevirus A, has seven genotypes[1].
The role of wild rodents and small mammals in the epidemiology of Hepatitis E Virus has been a subject of considerable debate. Time for a study, scientists decided.

A study was conducted to investigate the potential presence of Hepatitis E Virus in small rodents collected within their natural habitats and to detect if they can be potential reservoirs of the virus[2].

A total of 483 small rodents were captured using snap traps placed at a number of regions in Croatia. Sampling was undertaken in 2008 and repeated from 2010 to 2014. Liver samples were subsequently tested for the presence of Hepatitis E Virus.

Hepatitis E Virus was detected in only one liver sample from Yellow-necked Mouse (Apodemus flavicollis) collected near Zagreb in 2014.

According to the sequence analysis, the isolate has shown to be a member of Orthohepevirus A species, genotype HEV-3. The genotyping results confirmed grouping into subtype 3a.The detected Hepatitis E Virus strain showed to be genetically highly related to strains found in humans and/or domestic pigs and wild boars from Croatia.

The findings indicates that wild small mammals do play a possible role in the epidemiology of HEV-3 infection and therefore should be taken under consideration as potential reservoirs or/and transmitters of the disease. However, further investigation is needed to recognize their potential for maintaining the infection in natural conditions.

[1] Smith et al: Proposed reference sequences for Hepatitis E virus subtypes in Journal of General Virology – 2016. See here. [2] 
Prpić et al: First evidence of hepatitis E virus infection in a small mammal (yellow-necked mouse) from Croatia in PloS One – 2019. See here.

Hepatitis D Virus in Snakes

Hepatitis D Viruses form the genus Deltavirus that is unassigned to any virus family. So, it's a very lonely group of viruses. A Hepatitis D Virus is a so-called satellite virus and needs a Hepatitis B Virus to make infectious particles. Deltaviruses are thought to have evolved in humans, since for a long time, they had not been identified elsewhere.
Mother Nature always manages to surprise us, because recently a Hepatitis D Virus was discovered in birds[1]. Spurred on by this discovery scientists recently identified a novel Hepatitis D Virus in boa contrictors (Boa constrictor) and named it snake Hepatitis D Virus (shortened to SHDV)[2]. The scientists also detected snake Hepatitis D Virus RNA in a water python (Liasis mackloti savuensis) in the same snake colony, potentially indicating vertical and horizontal transmission.

Sequence comparison showed the snake Hepatitis D Virus antigen (sHDAg) to be 55% and 37% identical to its human and avian counterparts. However, the scientists were unable to detect accompanying Hepatitis B viruses, suggesting that snake Hepatitis D Virus could be a satellite virus of an (at the moment) unknown enveloped virus.

The identification of Hepatitis D Viruses in distantly related species other than humans indicates that the previously suggested hypotheses on the origins of Hepatitis D Viruses need to be updated.

[1] Wille et al: A divergent hepatitis D-like agent in birds in bioRxiv – 2018
[2] Hetzel et al: Identification of a Novel Deltavirus in Boa Constrictors in mBio - 2019

Hepatitis B Virus in Maxwell’s Duikers

If you needed further proof that Hepatitis B virusses are infecting man and animals all over the world, look no further. When six dead Maxwell’s duikers (Philantomba maxwellii), a small antelope, from Taï National Park, Côte d’Ivoire were examined, scientists found yet another novel hepadnavirus, the family of virusses that causes Hepatitis B infections[1].
Viral copy numbers in the blood of these dead Maxwell's Duikers were in the range known from humans with active chronic infections leading to liver damage, suggesting this virus could be pathogenic in duikers, though many orthohepadnaviruses appear to be apathogenic in other hosts.

Analysis placed the virus as a divergent member of the mammalian clade of orthohepadnaviruses, though its relationship to other orthohepadnaviruses remains uncertain. This represents the first orthohepadnavirus described in an artiodactyl (or even-toed ungulate), an order of mammals that includes pigs, peccaries, hippopotamuses, camels, chevrotains, deer, giraffes, pronghorn, antelopes, sheep, goats, and cattle. . The scientists have tentatively named this virus Taï Forest hepadnavirus.

The Taï Forest hepadnavirus is closely related to Hepatitis B Virus in woodchucks, the Hepatitis B Virus in arctic squirrels and Hepatitis B Virus in ground squirrels. These North American virusses now have a novel African family member.

[1] Gogarten et al: A Novel Orthohepadnavirus Identified in a Dead Maxwell’s Duiker (Philantomba maxwellii) in Taï National Park, Côte d’Ivoire in Virusses – 2019. See here.

Hepatitis B Virus sheds light on ancient human population movements into Australia

The precise moment of ancient human migration into continental Sahul (the combined landmass of Australia, New Guinea, and Tasmania) is still subject to debate.
Unique strains of Hepatitis B Virus are endemic among modern-day Australian Aboriginals (Hepatitis B Virus/C4)[1] and Indigenous Melanesians (Hepatitis B Virus/C3)[2]. Australian researchers have used current Hepatitis B Virus genome sequences to deduce ancient human population movements into Australia, adding weight to the theory that the mainland Aboriginal population separated from other early humans at least 59,000 years ago and possibly entered the country near the Tiwi Islands[3].

Chronic Hepatitis B Virus infection is endemic in Australian Aboriginal and Torres Strait Islander people and is an important cause of morbidity and mortality due to liver disease and liver cancer.

The research team collected Hepatitis B Virus samples from people living in over 30 communities across the Northern Territories and found Hepatitis B Virus isolated from Aboriginal Australians is a unique strain, known as HBV/C4, not found anywhere else in the world.

The researchers found that the precursor of the modern Hepatitis B Virus/C4 virus entered Australia over 51,000 years ago, and then separated into two groups; one centred in the northwest region, and a second in the central/eastern region of the Northern Territories. Strikingly, the two groups share a similar geographical distribution to the two main divisions of Aboriginal Australian languages spoken in Australia today.

The analysis also suggested that Hepatitis B Virus/C3 was carried into Melanesia by Indigenous Melanesians who migrated through New Guinea north of the highlands.

[1] Littlejohn et al: Molecular virology of hepatitis B virus, sub-genotype C4 in northern Australian Indigenous populations in Journal of Medical Virology - 2014
[2] Utsumi et al: Molecular epidemiological study of hepatitis B virus infection in two different ethnic populations from the Solomon Islands in Journal of Medical Virology - 2007
[3] Yuen et al: Tracing Ancient Human Migrations into Sahul Using Hepatitis B Virus Genomes in Molecular Biology and Evolution – 2019

Hepatitis B Virus treatment: the challenge

Hepatitis B Virus infections are extremely common around the world. About 257 million people are chronically infected, 80 million of whom live in China alone. As a direct result of their infection with Hepatitis B Virus, quite a sizable number of the individuals will go on to develop hepatocellular carcinoma, one of the deadliest forms of liver cancer. Worldwide, Hepatitis B Virus resulted in 887,000 deaths (2015)[1].
While vaccination is highly efficacious in preventing infection, vaccine coverage is incomplete and ongoing mother-to-child transmission contributes to the continued propagation of the disease. Although current Hepatitis B treatments effectively suppress viral replication, they are typically not curative. There is therefore a high unmet need for curative Hepatitis B Virus therapies.

However, research has shown that Hepatitis B Virus has a far higher mutation rate than previously thought. In a surprisingly short period of time, the virus effectively takes over the human cell's replication machinery in order to proliferate billions of viruses per day with every possible mutation represented[2]. With modern sequencing, these mutant viral strains, sometimes called 'quasispecies', can be precisely characterized.

You understand the problem: if a treatment is curative today, it might not be so tomorrow.

[1] WHO: Factsheet Hepatitis B. See here.
[2] Lin et al: New insights into the evolutionary rate of hepatitis B virus at different biological scales in Journal of Virology – 2015

Hepatitis A Virus in Marsupials

Hepatitis A Virus is a cause of acute viral hepatitis in humans, causing about 11,000 deaths worldwide per year. Hepatitis A Virus was long thought to be restricted to primates, with genotypes I to III found in humans and genotypes IV to VI, termed simian Hepatitis A Virus, found in nonhuman primates[1].
Only recently, highly diverse nonprimate hepatoviruses were discovered, suggesting that the ancestors of Hepatitis A Virus may have evolved in mammals other than primates prior to their introduction into humans. Additionally, the unique structural properties of Hepatitis A virusses, resembling those found in ancestral insect viruses, suggest that it is an ancient picornavirus[2].

The expanded genus Hepatovirus now includes at least 16 putative virus species. The majority of novel hepatoviruses were obtained from bats and rodents.

Now, scientists have discovered a novel marsupial Hepatitis A Virus in Brazilian common (or big-eared) opossum (Didelphis aurita)[3]. That is a potential problem, since opossums are commonly hunted and consumed as wild game by resource-limited (read: poor) Brazilian communities.

Because the family containing marsupial Hepatitis A Virus shares a common ancestor with human Human Hepatitis A Virus, it may hypothetically retain the ability to infect humans.

The results of this research strongly suggest that the species barriers toward Hepatitis A Virus infection seem penetrable.

[1] Cristina, Costa-Mattioli: Genetic variability and molecular evolution of hepatitis A virus in Virus Research - 2007
[2] Wang et al: Hepatitis A virus and the origins of picornaviruses in Nature - 2015
[x] de Oliveira Carneiro et al: A Novel Marsupial Hepatitis A Virus Corroborates Complex Evolutionary Patterns Shaping the Genus Hepatovirus in Journal of virology - 2018. See here.

Hepatitis B Virus in Crocodilians

Recently scientific research was published that reported that it had found – among others – endogenous viral elements (EVEs) from a Hepatitis B Virus in Crocodilians[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].

The scientists searched the recent saltwater crocodile, gharial, and American alligator draft genome assemblies using whole viral genomes of the duck Hepatitis B Virus and the Mesozoic endogenic Zebra finch Hepatitis B Virus (eZHBV) and identified two endogenous crocodilian Hepatitis B viruses (eCRHBVs): eCRHBV1 and eCRHBV2.

eCRHBV1 is present in all crocodilians except alligators and is 63.8–102.6 Millon Years (MY) old, which means that it is of Cretaceous origin. The second, eCRHBV2 is exclusively shared between saltwater and dwarf crocodiles: its endogenization thus occurred during the Paleogene in the ancestor of Crocodylidae (30.7–63.8 MYA).

So, the Hepatitis B Virus has been on the planet for millions of years. No wonder, then, that it has become so versatile. It changes, mutates and jumps species without any problem. As the Greek philosopher Heraclitus already said in the 4th century BC: There is nothing permanent except change.

[1] Suh et al: Early Mesozoic Coexistence of Amniotes and Hepadnaviridae in PloS Genetics - 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

The Seasonality of Hepatitis

Most of us are aware of the seasonal cycle of influenza outbreaks, which peak in the winter months. New research seems to show that all infectious diseases have a seasonal element.
Micaela Elvira Martinez, an assistant professor of Environmental Health Sciences, collected information from the World Health Organization, the U.S. Centers for Disease Control and Prevention, and peer-reviewed publications to create a calendar of epidemics for 69 infectious diseases. A given year will see outbreaks of flu in the winter, chickenpox in the spring, and gonorrhea and polio in the summer -- to name a few of the best described seasonal outbreaks.

She found seasonality occurs not just in acute infectious diseases like Influenza but also chronic infectious diseases like Hepatitis, which depending on geography, flares up with greater regularity certain times of the year[1].

The paper describes several drivers of seasonality in infectious diseases: (a) vector seasonality, (b) seasonality in nonhuman animal host (i.e., livestock, other domestic animals, or wildlife), (c) seasonal climate (e.g., temperature, precipitation, etc.), (d) seasonal nonclimatic abiotic environment (e.g., water salinity), (e) seasonal co-infection, (f) seasonal exposure and/or behavior and/or contact rate, (g) seasonal biotic environment (e.g., algal density in waterbodies), (h) seasonal flare-up/symptoms and/or remission/latency, (i) observed seasonal incidence with no hypotheses regarding drivers.

Let's see what Martinez' paper has to say about Hepatitis:
- Hepatitis A (Acute): seasonal drivers are (f) and (i) – Dry season (in Brasil)[2][3]
- Hepatitis B (Chronic): seasonal driver is (h) – Seasonality is observed with elevated levels in spring and summer and/or autumn in some parts of the world, whereas there is lack of seasonality in other parts of the world [3][4]
- Hepatitis C (Acute and Chronic): seasonal driver is (f) - Seasonality observed in some countries and absent in others; spring and/or summer peaks in Egypt, China, and Mexico while there is a winter peak in India[3]
- Hepatitis E (Acute): seasonal driver is (c) - Waterborne outbreaks occur during the rainy season or following flooding (in China)[5]

"Seasonality is a powerful and universal feature of infectious diseases, although the scientific community has largely ignored it for the majority of infections," says Martinez. "Much work is needed to understand the forces driving disease seasonality and understand how we can leverage seasonality to design interventions to prevent outbreaks and treat chronic infections."

[1] Micaela Elvira Martinez: The calendar of epidemics: Seasonal cycles of infectious diseases in PLoS Pathogens - 2018. See here.
[2] Bensabatb et al: Epidemiological and Serological Studies of Acute Viral Hepatitis in Brazil's Amazon Basin in Bulletin of the Pan American Health Organisation - 1987
[3] Fares: Seasonality of Hepatitis: A Review Update in Journal of Family Medicine and Primary Care - 2015. See here.
[4] Zhang et al: Effect of Seasonal Variation on the Clinical Course of Chronic Hepatitis B in Journal of Gastroenterology - 2006 
[5] Zhuang et al: Epidemiology of Hepatitis E in China in Gastroenterologia Japonica - 1991

A Novel Genotype of Hepatitis B Virus: J

As a result of continuous mutations and recombinations Hepatitis B Virus has evolved, much like Influenza A Virus, into several genotypes. Nine genotypes of Hepatitis B Virus (A-I) are currently recognized, and more and more subgenotypes have recently been described in five of these genotypes (A, B, C, D and F).
You might think that nine different genotypes are more than enough, but nature has decided otherwise. A novel genotype (J) was recovered from an 88-year-old patient from the Ryukyu Islands in Japan who had a history of 'residing' in Borneo during the World War II[1].

It was divergent from nine human (A to I) and four ape (chimpanzee, gorilla, gibbon and orangutan) Hepatitis B Virus genotypes. After further research it was found that this Hepatitis B Virus was genetically closer to gibbon and orangutan genotypes that other human genotypes. It was surmised that the man was infected during the Japanese occupation of in the Dutch East Indies during the World War II.

So, the scientists thought, if one person was infected by an ape and the Hepaptis B Virus adapted (read: mutated) itself to humans, there must be many more undetected infections. People and apes are often inhabiting the same environments.

[1] Tetematsu et al: A Genetic Variant of Hepatitis B Virus Divergent from Known Human and Ape Genotypes Isolated from a Japanese Patient and Provisionally Assigned to New Genotype J in Journal of Virology – 2009. See here.

Human Papillomavirus (HPV) linked to sex with Neanderthals

At least one version of the human papillomavirus (HPV), which leads to most cases of cervical cancer, evolved in humans as a result of sex with Neanderthal, a new study shows[1].
Although over 200 types of the virus exist,  just two — HPV16 and HPV18 — account for about 70 percent of all cervical cancers. HPV16 infection can also lead to anal cancer and cancers that develop in the throat, at the base of the tongue and the tonsils.

"There is not a more carcinogenic agent that causes cancer in humans than HPV, especially HPV16," said Robert Burk, who led the research.

As a medical geneticist Burk wanted to understand the genetics that drive the development of cancer. But there wasn’t a clear path to study how HPV contributes to the disease. So, he and his team began collecting as much information about the virus as possible.

In research published last year, Burk and colleagues analyzed the genetic sequences of HPV16 viruses from thousands of individuals and found that few women shared an identical form of the virus. It’s an indication that the virus has a knotty evolutionary past, and understanding might help shed light on why it can go on to cause cancer in some cases and not in others[2].

"It became clear that trying to study the viral genome and its association with cancer had to be viewed through the eyes of evolution," Burk said.

So, in the new study, Burk started with some of human’s closest evolutionary relatives, monkeys. The researchers isolated papillomaviruses from the oral, perianal and genital areas of squirrel and rhesus monkeys. When the scientists then compared the virus genomes, they found that the viruses that were most similar to each other came from the same parts of the body, meaning before papillomaviruses took up residence as cancer-causing parasites in humans, they first adapted to particular places in the body. The viruses then evolved within these niches for at least 40 million years.
To find out how the highly pathogenic HPV16 type of the virus evolved, the team then compared more than 200 complete HPV16 virus genomes and over 3,500 partial sequences isolated from around the world. When the researchers analyzed the virus’ evolutionary tree, they discovered that an ancient version of the virus split off onto its own evolutionary trajectory at about the same time modern humans separated from Neanderthals around 618,000 years ago. This version later evolved into four sub-types of HPV16 in Eurasian populations (ABCD lineages). The timing coincides with a split in Neanderthal populations that spread through Eurasia around 100 thousand years ago.

The finding suggests “genetic [versions] associated with cervix cancer in Northern European women appear to trace back to [the transfer of] Neanderthal genes through sexual intercourse between modern humans and archaic hominids,” Burk said. But it also “starts to provide an explanation for the differential carcinogenic potential of HPV16.”

[1] Chen et al: Niche adaptation and viral transmission of human papillomaviruses from archaic hominins to modern humans in PLoS Pathogens - 2018 
[2] Mirabello et al: HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis in Cell - 2017

Hepatitis E Virus in Rats

A taxonomic scheme was recently proposed in which the family of Hepatitis E viruses was divided into the genera Orthohepevirus (all mammalian and avian Hepatitis E viruses) and Piscihepevirus (cutthroat trout virus). Species within the genus Orthohepevirus are designated Orthohepevirus A (isolates from human, pig, wild boar, deer, mongoose, rabbit and camel), Orthohepevirus B (isolates from chicken), Orthohepevirus C (isolates from rat, greater bandicoot, Asian musk shrew, ferret and mink) and Orthohepevirus D (isolates from bat)[1].
Following the now accepted scheme, Hepatitis E Virus in rats is now called Hepatitis E Virus C-1, the first virus in the Orthohepevirus C sub-family. HEV-C1 strains can be divided into three genetic groups (G1, G2 and G3)[2].

So, Hepatitis E Virus has been found to infect rats. The question remained if this virus could infect humans. Test in laboratories suggested that it could, but now the first couple of human cases of rat Hepatitis E Virus have been reported.

[28sep18] The BBC reported: First human case of rat hepatitis found in Hong Kong

A 56-year-old man from Hong Kong has developed the world's first human case of rat hepatitis E. Researchers say it is unclear how the man contracted the virus, but refuse bins outside his home were infested with rats.

Doctors discovered the case when tests on the man showed abnormal liver function following a liver transplant. Further tests showed that he was carrying a strain of hepatitis "highly divergent" from the strain that affects humans, researchers from the University of Hong Kong said.

[21nov18] Outbreak News Today reported: Hong Kong reports 2nd human case of Rat Hepatitis E The Department of Health confirmed that the second patient was a retiree with underlying illnesses and a suppressed immune system.

[1] Smith et al: Consensus proposals for classification of the family Hepeviridae in Journal of General Virology – 2014
[2] Obana et al: Epizootiological study of rodent-borne hepatitis E virus HEV-C1 in small mammals in Hanoi, Vietnam in Journal of Veterinary Medical Science - 2017

Domestic Cat Hepatitis B Virus

While Domestic Cat Hepatitis B Virus is more properly called Domestic Cat Hepadnavirus, we will keep using the more accepted naming system.
A novel Hepatitis B Virus was discovered in a domestic cat from Australia[1]. In 2016, a seven year-old male-neutered domestic shorthair cat was presented for vomiting and weight loss. Diagnosed with Feline Immunodeficiency Virus (FIV), the cat was eventually euthanized.

To identify potential viral pathogens infecting domestic cats scientists performed high-throughput transcriptome sequencing of tissues from cats infected with Feline Immunodeficiency Virus (FIV).

During that investigation several cats, that had previously died as a result of FIV, also seemed infected with a virus. The virus itself was elusive and it showed only 73–94% amino acid identity with known Hepatitis B viruses. This suggested the presence of a novel virus that was divergent from currently known Hepatitis B viruses. Such a large genetic distance merits assignment of a new species within the genus Orthohepadnavirus, which was tentatively named Domestic Cat Hepadnavirus or Domestic Cat Hepatitis B Virus.

Further research revealed that it exhibited no close phylogenetic relationship to any other known Hepatitis B virusses.

[1] Aghazadeh et al: A Novel Hepadnavirus Identified in an Immunocompromised Domestic Cat in Australia in Virusses – 2018. See here.

Immune system does not recover despite cured Hepatitis C Virus infection

Changes to the immune system remain many years after a Hepatitis C Virus infection heals, a new study shows[1]. The findings increases understanding about chronic infection and the way it regulates and impacts composition of the immune system.

Infection with Hepatitis C Virus turns almost always chronic and poses a major health problem around the world. The infection can lead to cirrhosis and cancer of the liver when the immune system fails to fight the virus. Eventually the immune system becomes exhausted. Since a couple of years, however, most patients with Hepatitis C Virus can now be cured in a matter of a few weeks with revolutionary new medications.

The study included 40 patients with chronic Hepatitis C Virus infection whom researchers followed before, during and after treatment with these new medications to investigate impact on the composition and diversity of the immune system. Diversity is vital to the ability of the immune system to fight infections. Of particular importance are natural killer cells, a type of white blood cells. The researchers used flow cytometry and a new measurement method to derive the composition of the immune system, as well as the appearance of natural killer cells and their function in the blood.

“Researchers in the field previously focused on analysing individual components but were unable to draw any comprehensive conclusions,” says Niklas Björkström, who led the study. “The immune system is extraordinarily complex, incorporating a large number of interacting parts. We adapted new methods in order to assess and analyse that complexity in a fresh manner.”

The results showed that the overall composition of the immune system was affected by the chronic infection, with significantly reduced diversity among the natural killer cells. Many of the changes remained long after the virus had been eliminated by means of medication. Researchers have not yet determined the long-term implications but are currently exploring whether patients have a harder time fighting future infection.

Strunz et al: Chronic hepatitis C virus infection irreversibly impacts human NK cell repertoire diversity in Nature Communications - 2018

Hepatitis B Virus and Genghis Khan

The man who conquered almost the entire known world was originally called Temujin. It means 'of iron' in Mongolian and is derived ultimately from the old Turkish word temür ('iron'). We know him Genghis Khan(c. 1162-1227), the Mongol warrior who started life as a nomad in Mongolia. Later, his armies swept across the Asian steppes, conquering all they encountered. Only his timely death as a frail and sickly 65-year old Genghis Khan could arrest the hordes from reaching Europe.
Now, scientists found evidence that Mongol warriors from the steppe carried an early form of Hepatitis B Virus. Sequencing 304 genomes from the skeletons of people who lived on the steppe during the Iron and Bronze Ages (from about 2500 BC until 1200 AD), they found that twenty-five of the samples had DNA from Hepatitis B Virus in their bones[1].

That means that Hepatitis B Virus on the ancient steppes may have been as prevalent as it is in some of the most heavily impacted areas of the world today.
What the researchers found was that Hepatitis B Virus was circulating on the Eurasian steppes for thousands of years. One of the stains found is now extinct, having apparently faded out of existence sometime in the last 4,500 years. And one of the nine major genotypes circulating today appears to be the product of an ancient recombination between two strains of the Hepatitis B Virus.
[Novel genotypes A, B, C, D, E, F, G, H]
[Genotypes of Bronze Age and Iron Age]
Most of the genetic diversity in Hepatitis B viruses today probably arose sometime between 25,000 and 13,400 years ago, when the genetic lineages of Old World Hepatitis B strains and New World Hepatitis B strains split.

One modern strain, genotype A, was previously thought to have emerged in Africa and spread to the Americas and India within the last few centuries via the slave trade. But the researchers found some ancestral strains of type A in people living on the steppe as early as 4,300 years ago: some from the Sintasha culture in what is now southwest Russia, and one in a person from the Scythian culture in what is now Hungary.

That, suggests that it's the other way around, that it came from Europe, but it was introduced to South Asian populations historically recently.

[1] Mühlemann et al: Ancient hepatitis B viruses from the Bronze Age to the Medieval period in Nature – 2018

Stone Age and Medieval Hepatitis B Virus decoded

A team of researchers not only recovered ancient viral DNA from skeletons but also reconstructed the genomes of three strains of Hepatitis B Virus.
[Skeletal remains of HBV positive individual from the Stone Age site of Karsdorf (Germany). The individual was a male who died ataround 25-30 years. – Credit: Nicole Nicklisch]

For this study, the researchers analyzed samples from the teeth of 53 skeletons excavated from Neolithic and medieval sites in Germany[1]. The remains dated from around 5000 BC to 1200 AD. The researchers screened all samples for viral pathogens and detected ancient Hepatitis B Virus in three of the individuals. Full Hepatitis B Virus genomes were recovered from these samples, two of which were from the Neolithic period, dating to about 7000 and 5000 years ago, and one from the medieval period[2]. The Neolithic genomes represent the by far oldest virus genomes reconstructed to date.

Interestingly, the ancient virus genomes appear to represent distinct lineages that have no close relatives today and possibly went extinct. The two Neolithic genomes, although recovered from individuals that lived 2000 years apart, were relatively similar to each other in comparison with modern strains, and were in fact more closely related to modern strains of Hepatitis B Virus found in Chimpanzees and Gorillas. In contrast, the medieval Hepatitis B Virus genome is more similar to modern strains, but still represents a separate lineage. This is the case even when it is compared to two previously published Hepatitis B Virus genomes recovered from mummies dating to the 16th century. The Hepatitis B Virus strains found in these mummies are closely related to modern strains, suggesting a surprising lack of change in the virus over the last 500 years.
These findings point to a complicated history for the virus, which may have involved multiple cross-species transmission events.

[1] Ben Krause-Kyora et al: Neolithic and Medieval virus genomes reveal complex evolution of Hepatitis B in eLife – 2018
[2] Patterson Ross et al: The paradox of HBV evolution as revealed from a 16th century mummy in PloS Pathogens - 2018

Hepatitis A Virus in Molluscs

Hepatitis A Virus is primarily spread when an uninfected and unvaccinated person ingests food or water that is contaminated with the faeces of an infected person. The disease is closely associated with unsafe water or food, inadequate sanitation and poor personal hygiene. When you are infected with Hepatitis A virus, you might experience some rather unpleasant symptoms. These include fever, malaise, loss of appetite, diarrhoea, nausea, abdominal discomfort, dark-coloured urine and jaundice (a yellowing of the skin and whites of the eyes). Not everyone who is infected will have all of the symptoms.
One of the places you might venture into quite frequently when you have diarrhoea is the toilet. In several countries faeces still is led untreated into the sea. So, the question is therefore, is Hepatitis A Virus able to infect (edible) molluscs.

Scientists studied of a total of 352 samples, including four bivalve mollusc species, the Mediterranean mussel (Mytilus galloprovincialis), the European razor clam (Solen vagina), the striped venus clam (Venus gallina) and the abrupt wedge shell (Donax trunculus). Hepatitis A Virus was detected in 77 samples[1]. All of these molluscs are consumed in the Mediterranean.

If you like to eat your molluscs raw, you should be aware that you could become infected with Hepatitis A Virus.

[1] Suffredini et al: Occurrence and Trend of Hepatitis A Virus in Bivalve Molluscs Production Areas Following a Contamination Event in Food and Environmental Virology - 2017

Hepatitis E Virus in Namibia

During the week ending on 13 October 2017, the first identified case was admitted to a public hospital in Windhoek district, with signs and symptoms of hepatitis E. During the week ending on 8 January 2018, a total of 237 probable and confirmed cases have been seen at various health facilities in Windhoek district with the same signs and symptoms. All suspected patients tested negative for hepatitis A, B, and C. A total of 41 of the 237 cases were sent for further testing, and on 8 January 2018, the results showed 21 were IgM positive for hepatitis E. On 19 November 2017, there was one confirmed deceased case, a 26 year-old female. Four days prior to her death she had delivered a baby. The status of the baby is unknown. The majority of the cases were from Windhoek district, Khomas region.
[The number of patients seen with acute clinical jaundice in Windhoek district by week, from September 2017 to 8 January 2018 (n = 237)]

Although infections with Hepatitis A, B and C are common in Namibia, Hepatitis E is rarely diagnosed in the country. As a result, the country has limited capacity for hepatitis E laboratory diagnosis. Additionally, the majority of hepatitis E cases have been reported from informal settlements within the capital district, Windhoek, where living conditions are poor. These areas are overcrowded, have limited access to safe drinking water, sanitation and hygiene.

Moreover, the holiday season will likely increase the movement of people within the country. All of these could be major contributing factors to this outbreak.

Additionally, during the rainy season, people often use rainwater or other surface water for drinking and domestic uses. This likely increases the risk of hepatitis E infection. Therefore, the above-mentioned factors might lead to the propagation of the cases from this area to other informal settlements and its distribution to other towns or districts, with similar poor environmental health conditions. Thus, the overall risk is assessed as high at the national level and low at regional and global levels.

Hepatitis B Virus in 16thC Mummified Child

Little is known about the evolutionary history and origin of Hepatitis B Virus. Recent research confirms the idea that Hepatitis B Virus has existed in humans for centuries[1]. Scientists extracted genomic data extracted from the mummified remains of a child buried in the Basilica of Saint Domenico Maggiore in Naples (Italy).
Previous scientific analysis of the 16th century (radiocarbon dating is AD1569±60) remains suggested the child was infected with Variola virus, or smallpox[2]. In fact, this was the oldest evidence for the presence of smallpox in Medieval remains and a critical time stamp for its origins.

Using advanced sequencing techniques, researchers now suggest otherwise: the child was actually infected with Hepatitis B Virus. Interestingly, children infected with Hepatitis B Virus infections can develop a facial rash, known as Gianotti-Crosti syndrome. This may have been misidentified as smallpox and illustrates the difficulties of identifying infectious disease in the past.
“The data emphasizes the importance of molecular approaches to help identify the presence of key pathogens in the past, enabling us to better constrain the time they may have infected humans,” explains Hendrik Poinar, an evolutionary geneticist. “The more we understand about the behaviour of past pandemics and outbreaks, the greater our understanding of how modern pathogens might work and spread, and this information will ultimately help in their control,” says Poinar.

Using small tissue samples of skin and bone, scientists were able to tease out tiny fragments of DNA and then stitch together pieces of genetic information to create a much more complete picture.

While viruses often evolve very rapidly - sometimes in just days - researchers suggest that this ancient strain of Hepatitis B Virus has changed little over the last 450 years and that the evolution of this virus is complex.

The team found a close relationship between the ancient and modern strains of Hepatitis B Virus, but both are missing what is known as temporal structure. In other words, there is no measurable rate of evolution throughout the 450-year period which separates the mummy sample from modern samples.

[1] Patterson Ross et al: The paradox of HBV evolution as revealed from a 16th century mummy in PloS Pathogens - 2018
[2] Marennikova et al: Smallpox diagnosed 400 years later: results of skin lesions examination of 16th century Italian mummy in Journal of Hygiene, Epidemiology, Microbiology and Immunology - 1990

Hepatitis C Virus and Opioid Abuse

New research suggests that the recent steep increase in cases of acute Hepatitis C Virus infection is associated with increases in opioid injection[1]. Across the nation, researchers found substantial, simultaneous increases in acute Hepatitis C (+133 percent) and admissions for opioid injection (+93 percent) from 2004 to 2014. These increases were seen at not only the national level, but also when data were analysed by state, by age, by race and ethnicity. Taken together, the findings point to a close relationship between the two troubling trends.

For an analyses about the opioid crisis, see here and here.
About 75 to 85 percent of newly infected people develop a chronic Hepatitis C Virus infection. As there are few noticeable symptoms, many people are unaware of their infection until serious liver problems or other health issues arise. Hepatitis C is therefore a potentially deadly and often invisible result of America’s opioid crisis.

The new analysis builds upon earlier research identifying a similar regional trend in four Appalachian states that faced increasing rates of new Hepatitis C Virus infection[2].

Hepatitis C is spread through infected blood, which can contain high levels of the virus in a single drop. This, combined with needle and injection equipment sharing behaviours among some people who inject drugs, is fuelling infections among younger Americans.

Until recently, Hepatitis C primarily affected older generations, but as the opioid crisis worsened, the virus gained a foothold among younger Americans. Most of the 3.5 million people in the United States already living with Hepatitis C are born between 1945 and 1965, but the greatest increases in new infections are being seen in young people. And as infections increase among young women, so has the rate of Hepatitis C among pregnant women, placing a new generation at risk.

[1] Zibbell et al: Increases in Acute Hepatitis C Virus Infection Related to a Growing Opioid Epidemic and Associated Injection Drug Use, United States, 2004 to 2014 in American Journal of Public Health – 2017
[2] Zibbell et al: Increases in Hepatitis C Virus Infection Related to Injection Drug Use Among Persons Aged ≤30 Years — Kentucky, Tennessee, Virginia, and West Virginia, 2006–2012 in Morbidity and Mortality Weekly Report (MMWR) – 2015. See here.

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, compared to Hepadnaviriruses.
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.

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