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Sci Transl Med. 2015 Sep 16;7(305):305ra144. doi: 10.1126/scitranslmed.aab3467.

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

Author information

1
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
2
Wisconsin National Primate Research Center, Madison, WI 53711, USA.
3
Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
4
Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo 01310-911, Brazil.
5
Wisconsin National Primate Research Center, Madison, WI 53711, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
6
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA. doconnor@primate.wisc.edu.

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.

PMID:
26378244
PMCID:
PMC4605385
DOI:
10.1126/scitranslmed.aab3467
[Indexed for MEDLINE]
Free PMC Article

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