Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection
| Autor: | Kerry A Beheler, David H. O’Connor, Gabrielle Lehrer-Brey, Michael Lauck, Adam L. Bailey, Jeffrey Rogers, Saverio Capuano, Kristin Crosno, Andrea M. Weiler, Heather A. Simmons, Justin M. Greene, Eric J. Peterson, Kevin Brunner, Mariel S. Mohns, Andres Mejia, James Mutschler, Tony L. Goldberg, Thomas C. Friedrich, Samuel D. Sibley, Matthew Gehrke, Adam J. Ericsen, Esper G. Kallas |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pegivirus Population GB virus C HIV Infections Viremia Macaque Article Virus Evolution Molecular Bone Marrow biology.animal medicine Animals Humans education Phylogeny Acquired Immunodeficiency Syndrome Likelihood Functions education.field_of_study biology Reverse Transcriptase Polymerase Chain Reaction Genetic Variation High-Throughput Nucleotide Sequencing General Medicine Flaviviridae Infections Viral Load biology.organism_classification medicine.disease Virology Disease Models Animal Viral Tropism Immunology Tissue tropism Macaca RNA Viral Female Viral load Papio |
| Zdroj: | Science Translational Medicine. 7 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | Human Pegivirus (HPgV) – formerly known as GB virus C and hepatitis G virus – is a poorly characterized RNA virus that infects approximately one-sixth of the global human population and is transmitted frequently in the blood supply. Here, 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 upon 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 the majority of 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. |
| Databáze: | OpenAIRE |
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