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Study Suggests Bats May Be Common Reservoir for Hepatitis C-related Viruses

NEW YORK (GenomeWeb News) - Bats can carry a wide range of viral representatives resembling hepatitis C virus, a new study suggests.

In the early, online version of the Proceedings of the National Academy of Sciences this week, an international group led by investigators at Columbia University used RNA sequencing to look at the sorts of viruses found in blood samples from hundreds of bats collected in Africa and Central America.

The search led to dozens of viruses with sequences resembling hepatitis C and related viruses from the same family, including so-called GB-viruses or pegiviruses. And when they expanded their search to more than 1,200 additional bats from various locales around the world, researchers consistently found both hepaciviruses and pegiviruses in a subset of sampled bats, hinting that the animals may be a possible source of viruses involved in human infections.

"The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses," senior author Ian Lipkin, with the center for infection and immunity at Columbia University's Mailman School of Public Health, and colleagues wrote, "and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses."

Past research suggests that the forms of hepatitis C and related viruses that infect humans could have emerged from one or more wild animal sources, though the nature and extent of the hepatitis-related viral wildlife reservoir has remained difficult to determine.

At the same time, studies have started to reveal the wide range of viruses that successfully use bats as a host, Lipkin and his co-authors noted, indicating that a more intense examination of the more than 1,100 species making up the bat order (Chiroptera) might unearth viruses with ties to those infecting humans.

"Bats possess unique characteristics that may contribute to their capacity to function as a major reservoir host for viruses," they wrote, "including long lifespan, high species diversity, unique immune systems, gregarious roosting behaviors, and high spatial mobility and population densities."

For their PNAS analysis, the researchers began by performing Roche 454 sequencing on pooled samples of RNA isolated from the blood of 415 bats collected in Guatemala, Cameroon, Nigeria, Kenya, and the Democratic Republic of the Congo.

The team then tallied up the RNA and amino acid sequences left in the resulting reads once bat sequences had been tossed out — a search that led them to viral sequences most closely related to viruses in the Flaviridae family.

Those viruses showed varying degrees of similarity to two genera in particular, researchers reported: Hepacivirus — the genus to which hepatitis C belongs — and Pegivirus.

The original bat samples contained some 58 such viruses. But investigators tracked down even more hepacivirus- and pegivirus-related sequences when they did targeted PCR-based screens on another 1,200 or so bats from various species in seven countries.

All told, the team found hepaciviruses and/or pegiviruses in almost 5 percent of bats tested. And a phylogenetic analysis of 83 viral representatives identified in bats revealed viral diversity that overlapped with that of viruses described in human or primate infections.

For their follow-up analyses, meanwhile, researchers managed to put together almost complete genome sequences for 20 of the bat-derived viruses, making it possible to look at the general organization of the genomes as well as the coding repertoire of the bat-borne viruses.

Together, authors of the study argued, the "prevalence, unprecedented viral biodiversity, and broad geographic distribution of these viruses, identified throughout the order Chiroptera, suggest that bats are a key natural reservoir for both hepaciviruses and pegiviruses."

"Additional field surveillance for these hepaci- and pegiviruses in other mammalian taxa will be necessary to unveil the diversity, biogeography, epizootiology, and natural history of these viruses," they concluded, "as well as the mechanisms that drive spill-over infections and host shifts."

In work published earlier this month in mBio, meanwhile, Lipkin led another group of investigators who identified and characterized hepaciviruses and pegiviruses in wild rodents.

Prior to that, most hepacivirus infections had been identified in the primate lineage, though horse and dog hosts have also been documented. This spring, for instance, a PNAS study found a Hepacivirus and Pegivirus-related virus in horses with a form of hepatitis known as Theiler disease.

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