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J Gen Virol. 2014 Jun;95(Pt 6):1307-1319. 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
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
2
Medicine Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52246, USA.
3
Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
AIDS Research Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
5
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.

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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