Holy Virus Treasure Trove, Batman!

Think about the type of animal that would make an ideal host for a virus. It would gather in large dense groups, making it easier for the virus to jump into fresh hosts. It should have a relatively long lifespan, so any single individual has many chances of becoming infected. It would certainly travel over long distances to spread the infection far and wide. Humans certainly fit the bill. So do bats.

At least one in every five mammal species is a bat. These diverse fliers—all 1,200 species of them—are reservoirs for an equally diverse group of viruses, including many deadly celebrities that can jump into humans. Bats carry rabies. They harbour SARS and other coronaviruses. They’ve got Nipah virus and Hendra virus, mumps, Marburg, and possibly Ebola.

Now, a team of virus-hunters led by Ian Lipkin from Columbia University has found that bats are also treasure troves for two little-known viral groups—hepaciviruses and pegiviruses. There’s no evidence that these new bat viruses could infect humans, but they could help to explain the origins of others that can.

The most famous hepacivirus is the hepatitis C virus (HCV), which causes liver disease, cirrhosis and liver cancer. It is transmitted through sex and shared blood and is found in around 3 percent of people around the world. HCV was discovered more than 20 years ago but we still don’t know where it came from. The same goes for its relatives, which can infect chimps, monkeys, dogs and horses.

The pegiviruses are even more mysterious. These species, with unremarkable names like GBV-A, GBV-C and GBV-D, have only been identified within the last decade. One of the most recent discoveries—TDAV—may cause a mysterious liver disease in horses that has puzzled vets for a century. When I reported on TDAV in March, one of my sources hinted that “studies on new pegiviruses may be published in the future”. He was right. Just last week, Lipkin’s team announced another new pegivirus from horses.

Now, they’ve shown that these known viruses are just twigs of a lush family tree, one that has been sprouting new trunks and branches in other animals for a very long time.

For a start, they identified seven new hepaciviruses and pegiviruses in wild rodents such as deer mice. That’s important for scientists studying hepatitis C virus. Animal viruses have a long history of helping us understand our own infections. Scientists have used SIV, which infects chimps and monkeys, to study HIV. The cowpox virus led to a vaccine for smallpox. But HCV has no good animal counterpart, and it doesn’t infect rats or mice.

Until now, chimps were the only animals that could be infected with HCV in experiments, and such research is ethically contentious, expensive, and being phased out. Lipkin hopes that his newly discovered rodent hepaciviruses could finally provide an analogue of HCV that can be easily studied in the lab, perhaps leading to new vaccines or treatments.

“In the rodents, our focus was on finding any hepacivirus that was really similar [to HCV],” says Lipkin. By contrast, the goal with the bats was to explore far and wide. “What we did with the bats was more like astronomy,” he says.

Phenix-Lan Quan led the work, which involved searching for new hepaciviruses and pegiviruses in 1,673 blood samples collected by other scientists working in 7 tropical countries. The samples came from 57 species of bats and yielded 83 viruses—including 3 new hepaciviruses and 19 new pegiviruses. These new viruses included some that are so dissimilar from the ones we knew about that their proteins share only a quarter of their amino acids. “It dramatically changes our whole view of these viruses,” says Lipkin. “There’s such extraordinary diversity among them.”

Between them, the two groups of viruses infected nearly five percent of the individual bats in the study (to no obvious ill effect), including those from 20 species and three continents. The similarities between them showed bizarre patterns that could only be explained by a long history of species-hopping and long-distance travel. For example, many of the pegiviruses in Bangladeshi bats were more closely related to those in African bats than they were to each other.

“It takes a long time to generate that sort of diversity,” says Lipkin. “And in humans, there’s very little diversity.” The implication is that these viruses have been diversifying in bats for much of their evolutionary history, and only recently made the jump into humans. Our experience with other bat diseases suggests how these jumps might have happened. Maybe, as with Nipah virus, people became infected by eating food contaminated by bat faeces or meat from infected livestock. Perhaps, as was possibly the case for SARS, the viruses passed from bats to us via animals in crowded Chinese “wet markets”.

These stories are possible, but we still don’t know if bats were the original source of hepaciviruses and pegiviruses (even if the team’s results are furtively pointing a finger in that direction and coughing slightly). We’ll only get clearer answers through studies in other animal groups and, indeed, of more bats from Asia and other continents.

Meanwhile, Quan says, “It is important to understand that there’s no evidence that these viruses are transmitted directly to humans. “She is concerned that people will take her study to mean that bats are threats to public health, and points out that they play important roles as pollinators and insect predators. “Their ecological benefits far outbalance their potential for disease transmission.”

When bats have donated diseases to humans, it’s often because their habitats have been disturbed, either by changing climates or our own encroaching activities. The key to preventing these spillovers, says Quan, is “to gain a better understanding of the ecology of bats and the range of infectious agents that are associated with them”. That could drive active monitoring programmes and to set up efforts to conserve the animal’s natural habitat.

Update: A late-arriving opinion from Linfa Wang, a virologist at Duke-NUS: he believes that in terms of using these new viruses to guide animal research into possible treatments, “there is still a long way to go and the significance of the current discoveries remains to be seen.” But the studies are highly important in showing that bats are reservoirs for these diverse and ancient viruses. Others including Wang have seen similar patterns for other virus families, but never these ones.

Reference Quan, Firth, Conte, Williams, Zambranan-Torrelio, Anthony, Ellison, Gilbert, Kuzmin, Niezgoda, Osinubi, Recuenco, Markotter, Breiman, Kalemba, Malekani, Lindblade, Rostal, Ojeda-Flores, Suzan, Davis, Blau, Ogunkoya, Alvarez Castillo, Moran, Ngam, Akaibe, Agwanda, Briese, Eptein, Daszak, Rupprecht, Holmes & Lipkin. 2013. Bats are a major natural reservoir for hepaciviruses and pegiviruses. PNAS http://dx.doi.org/10.1073/pnas.1303037110

Kapoor, Simmonds, Scheel, Hjelle, Cullen, Burbelo, Chauhan, Duraisamy, Leon, Jain, Vandegrift, Calisher, Rice & Lipkin. 2013. Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses. mBio http://dx.doi.org/10.1128/mBio.00216-13

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