Phopivirus: Hepatitus A Virus' Newly Discovered Cousin

By: Helen Beilinson

As Zuri has written about before, seals may have been the original carriers of the bacterium that causes tuberculosis, Mycobacterium tuberculosis. Seals may get another bad hit to their name with a new paper showing that harbor seals have a unique virus called phopivirus, which is closely related to the human virus hepatitis A virus (HAV). The discovery of this virus provides a broader picture of the viral diversity within the HAV family.

HAV, as the name suggests, is the causative agent of hepatitis A. HAV infects hepatocytes and Kupffer cells, causing major liver inflammation, leading to nausea, jaundice, and dark, amber-colored urine. Hepatitis A has been evolving with humans for a while now, but it’s not clear when and from where the virus first emerged in the human population.

In a somewhat strange incident in 2011, many harbor seals (Phoca vitulina vitulina) were dying from pneumonia all along the coast of New England. To identify the pathogen that was responsible, scientists isolated lungs, livers, spleens, and oral mucosa (by taking a cheek swab) from three harbor seals that passed by this infectious agent. By isolating the genetic material from these samples, the scientists were able to identify viruses that had infected the isolated tissues. Not only did the samples reveal that the seals’ pneumonia was probably caused by an influenza virus infection (the stain, H3N8, had been circulating around the United States at the time), further studies showed that a previously unidentified virus was also in these tissues. By comparing the genome of this new virus to known viruses, the authors were able to characterize this new virus, phopivirus, as HAV’s closely related cousin.

The authors continued to characterize the virus in the hopes that it would provide more information as to the natural history of HAV. There are a few ways in which such a closely related virus could have emerged in the seal population. First, there could have been a transfer of HAV from humans to seals. Second, there could have been a zoonotic transmission of phopivirus from seals to human. Or, third, the two viruses may have both evolved from a common ancestral virus that both infected humans and seals independently, and within each speices, the virus evolved into the HAV and phopivirus we see today.

Like all pathogens, viruses evolve in conjunction with their hosts to in an attempt to survive within the host for as long as possible and to avoid the hosts’ attempts to eliminate them. This leads to the observation that when viruses have been in a host for many generations, the virus evolves to function ideally within that particular host. When this virus jumps from one host to a new one, the virus must then adapt fairly quickly to adjust to the new host, such that after the jump occurs, the virus has a very rapid burst of adaptive evolution. To identify whether phopivirus has evidence of adaptive selection, the authors looked at two genes within the viral genome (VP1 and 3D) and performed a particular algorithm that compares the genes’ sequences in phopivirus to other viral strains to evaluate whether rapid diversification of the genes had occurred. In addition to this algorithm, the authors looked at various tissue samples from 29 other harbor seals and six gray seals. In eleven of the harbor seals and one of the gray seals, the authors not only found phopivirus, but found that the VP1 and 3D genes were dearly identical, which complies with the conservative nature of VP1 and 3D (meaning that these genes tend to not mutate much once the virus has established itself within a new host population). From these results, the authors conclude that seals are the natural host of phopivirus and that the virus has been evolving in the seals for a long period of time, and had not been introduced recently, eliminating the hypothesis that HAV has been transmitted to seals or that phophivirus was zoonotically transmitted to humans.

Phopivirus is the closest related virus to HAV ever discovered, and, in fact, is the first known liver-infecting virus found outside of primates. The authors of this study argue that the two viruses have very similar origins, and that differences within their genomes are due to the evolutionary constraints on the viruses within their distinct hosts. Based on these data, it cannot be concluded that there was no transmission of either virus from human to seal (or vice versa). A previous hypothesis on the origin of HAV was that an Old World nonhuman primate zoonotically transmitted the virus to humans. This hypothesis also cannot be discarded with these new data. More studies will have to be to done to further understand the history of the HAV family, but seals have proved that the HAV family is must more diverse than previously thought.