title: Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Bailey
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lauck
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Mariel
authors.initials: M
authors.lastname: Mohns
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Peterson
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Beheler
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Brunner
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Crosno
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Mejia
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: James
authors.initials: J
authors.lastname: Mutschler
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gehrke
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Greene
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA. Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ericsen
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Weiler
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Lehrer-Brey
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Sibley
authors.affiliation: Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo 01310-911, Brazil.
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Saverio
authors.initials: S
authors.lastname: Capuano
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rogers
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Tony L
authors.initials: TL
authors.lastname: Goldberg
authors.affiliation: Wisconsin National Primate Research Center, Madison, WI 53711, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Simmons
authors.affiliation: 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.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D005260:Female; D018178:Flaviviridae Infections / Q000150:complications*; D029407:GB virus C; D014644:Genetic Variation; D015658:HIV Infections / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016013:Likelihood Functions; D008251:Macaca; D008297:Male; D010215:Papio; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D056189:Viral Tropism; D014766:Viremia
chemical_list: D012367:RNA, Viral