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J Gen Virol. 2014 Jun;95(Pt 6):1307-19. doi: 10.1099/vir.0.063016-0. Epub 2014 Mar 25.

Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and serum-derived viral RNA-containing particles are infectious in vitro.

Author information

1
Medicine Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52246, USA Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
2
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
3
AIDS Research Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Medicine Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52246, USA Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA jack-stapleton@uiowa.edu.

Abstract

Human pegivirus (HPgV; previously called GB virus C/hepatitis G virus) has limited pathogenicity, despite causing persistent infection, and is associated with prolonged survival in human immunodeficiency virus-infected individuals. Although HPgV RNA is found in and produced by T- and B-lymphocytes, the primary permissive cell type(s) are unknown. We quantified HPgV RNA in highly purified CD4(+) and CD8(+) T-cells, including naïve, central memory and effector memory populations, and in B-cells (CD19(+)), NK cells (CD56(+)) and monocytes (CD14(+)) using real-time reverse transcription-PCR. Single-genome sequencing was performed on viruses within individual cell types to estimate genetic diversity among cell populations. HPgV RNA was present in CD4(+) and CD8(+) T-lymphocytes (nine of nine subjects), B-lymphocytes (seven of ten subjects), NK cells and monocytes (both four of five). HPgV RNA levels were higher in naïve (CD45RA(+)) CD4(+) cells than in central memory and effector memory cells (P<0.01). HPgV sequences were highly conserved among subjects (0.117±0.02 substitutions per site; range 0.58-0.14) and within subjects (0.006±0.003 substitutions per site; range 0.006-0.010). The non-synonymous/synonymous substitution ratio was 0.07, suggesting a low selective pressure. Carboxyfluorescein succinimidyl ester (CFSE)-labelled HPgV RNA-containing particles precipitated by a commercial exosome isolation reagent delivered CSFE to uninfected monocytes, NK cells and T- and B-lymphocytes, and HPgV RNA was transferred to PBMCs with evidence of subsequent virus replication. Thus, HPgV RNA-containing serum particles including microvesicles may contribute to delivery of HPgV to PBMCs in vivo, explaining the apparent broad tropism of this persistent human RNA virus.

PMID:
24668525
PMCID:
PMC4027039
DOI:
10.1099/vir.0.063016-0
[Indexed for MEDLINE]
Free PMC Article

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