Hepatitis D Virus: The search for its origins

Hepatitis D Virus is a so-called 'satellite'. These are a peculiar group of virus-like agents that hijack unrelated viruses (called their 'helpers') to spread. Satellites often makes the disease caused by their helper viruses more severe.

The origins of Hepatitis D Virus have long been a mystery. Having an animal origin has seemed unlikely because the ancestor satellite would either need to bring along its old helper or switch to a new and unfamiliar helper in humans. Both options add a degree of difficulty that normal viruses don't have to deal with.

Recently, studies have discovered relatives of Hepatitis D, known as Deltaviruses, in a diverse range of animals including fish, amphibians and termites. This suggests the possibility that Hepatitis D-like satellites could jump between animals more easily than thought[1].

Hepatitis D Virus is the only satellite known to cause illness in humans. Hepatitis D Virus exploits the Hepatitis B Virus, to enter and exit cells, and in the process causes the most severe form of viral hepatitis in 20 million people worldwide.

A recent study discovered new, close animal relatives of Hepatitis D, meaning that it is a zoonotic disease[2]. The virus passed from animals to humans and then slowly travelled around the world. As a result, hepatitis D can now be found on all continents.

All new Deltaviruses found—along with one recently discovered in rats from Panama – came from the Americas[3]. This was unexpected because Hepatitis D was previously thought to have originated somewhere in Africa.

So, the arrival of Hepatitis B (a compatible human helper for Hepatitis D) to the Americas via human migration might have facilitated Hepatitis D's leap into humans.

Deltaviruses have made jumps between non-human mammals. One Deltavirus from a lesser dog-like bat from Mexico was most similar to Deltaviruses from spiny rats in Panama[3]. Meanwhile, two different Deltaviruses were discovered in common vampire bats from Peru that were not closely related to one another or the other bat Deltavirus. Multiple non-human mammal jumps show that this host-leaping habit is a rule rather than an exception for Deltavirus evolution.

Exactly which helpers are used by the new animal-infecting deltaviruses is still a mystery, but viruses related to Hepatitis C Virus are emerging as strong candidates after being found in bat and rodent hosts along with Deltaviruses. Regardless, the absence of Hepatitis B-related helpers revealed another piece of the Hepatitis D origin puzzle: somewhere along the journey into humans, the forebear of Hepatitis D switched helpers, acquiring the modern association with Hepatitis B.

[1] Chang et al: Novel hepatitis D-like agents in vertebrates and invertebrates in Virus Evolution - 2019
[2] Bergner et al: Diversification of mammalian deltaviruses by host shifting in PNAS – 2021
[3] Paraskevopoulou et al: Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus in PNAS - 2020