Research ArticleVirology

Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection

Science Translational Medicine  16 Sep 2015:
Vol. 7, Issue 305, pp. 305ra144
DOI: 10.1126/scitranslmed.aab3467

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An animal model for the “Good Boy Virus”

Human pegivirus (HPgV, formerly called GB virus C) can protect HIV-infected individuals from developing AIDS, a phenomenon that has earned it the nickname of the “Good Boy Virus.” How HPgV imparts this protective effect remains a mystery, in part because no animal model of HPgV infection exists. Bailey and colleagues discovered viruses related to HPgV in wild baboons and showed that these viruses can infect laboratory macaque monkeys, providing unprecedented insights into the transmission, replication, and anatomical preference of HPgV with a view towards understanding HPgV-mediated protection from AIDS.

Abstract

Human pegivirus (HPgV)—formerly known as GB virus C and hepatitis G virus—is a poorly characterized RNA virus that infects about one-sixth of the global human population and is transmitted frequently in the blood supply. We create an animal model of HPgV infection by infecting macaque monkeys with a new simian pegivirus (SPgV) discovered in wild baboons. Using this model, we provide a high-resolution, longitudinal picture of SPgV viremia where the dose, route, and timing of infection are known. We detail the highly variable acute phase of SPgV infection, showing that the viral load trajectory early in infection is dependent on the infecting dose, whereas the chronic-phase viremic set point is not. We also show that SPgV has an extremely low propensity for accumulating sequence variation, with no consensus-level variants detected during the acute phase of infection and an average of only 1.5 variants generated per 100 infection-days. Finally, we show that SPgV RNA is highly concentrated in only two tissues: spleen and bone marrow, with bone marrow likely producing most of the virus detected in plasma. Together, these results reconcile several paradoxical observations from cross-sectional analyses of HPgV in humans and provide an animal model for studying pegivirus biology.

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