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

TitleDurable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsBailey, AL, Lauck, M, Mohns, M, Peterson, EJ, Beheler, K, Brunner, KG, Crosno, K, Mejia, A, Mutschler, J, Gehrke, M, Greene, J, Ericsen, AJ, Weiler, A, Lehrer-Brey, G, Friedrich, TC, Sibley, SD, Kallas, EG, Capuano, S, Rogers, J, Goldberg, TL, Simmons, HA, O'Connor, DH
JournalSci Transl Med
Volume7
Issue305
Pagination305ra144
Date Published2015 Sep 16
ISSN1946-6242
KeywordsAcquired Immunodeficiency Syndrome, Animals, Bone Marrow, Disease Models, Animal, Evolution, Molecular, Female, Flaviviridae Infections, GB virus C, Genetic Variation, High-Throughput Nucleotide Sequencing, HIV Infections, Humans, Likelihood Functions, Macaca, Male, Papio, Phylogeny, Reverse Transcriptase Polymerase Chain Reaction, RNA, Viral, Viral Load, Viral Tropism, Viremia
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.

DOI10.1126/scitranslmed.aab3467
Alternate JournalSci Transl Med
PubMed ID26378244
PubMed Central IDPMC4605385
Grant ListR01 TW009237 / TW / FIC NIH HHS / United States
C06 RR020141 / RR / NCRR NIH HHS / United States
C06 RR015459 / RR / NCRR NIH HHS / United States
P51 RR000167 / RR / NCRR NIH HHS / United States
RR15459-01 / RR / NCRR NIH HHS / United States
T32 GM081061 / GM / NIGMS NIH HHS / United States
RR020141-01 / RR / NCRR NIH HHS / United States
R01 AI084787 / AI / NIAID NIH HHS / United States
R01 AI077376 / AI / NIAID NIH HHS / United States
P51RR000167 / RR / NCRR NIH HHS / United States
T32 GM008692 / GM / NIGMS NIH HHS / United States
TW009237 / TW / FIC NIH HHS / United States
T32 AI078985 / AI / NIAID NIH HHS / United States
T32 AI055397 / AI / NIAID NIH HHS / United States
T32GM081061 / GM / NIGMS NIH HHS / United States
P51 OD011106 / OD / NIH HHS / United States
T32 AI55397 / AI / NIAID NIH HHS / United States