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

被引:67
作者
Chivero, Ernest T. [1 ,2 ]
Bhattarai, Nirjal [1 ,2 ]
Rydze, Robert T. [2 ]
Winters, Mark A. [3 ,4 ]
Holodniy, Mark [3 ,4 ]
Stapleton, Jack T. [1 ,2 ,5 ]
机构
[1] Iowa City Vet Affairs Med Ctr, Med Serv, Iowa City, IA 52246 USA
[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[3] VA Palo Alto Hlth Care Syst, AIDS Res Ctr, Palo Alto, CA 94304 USA
[4] Stanford Univ, Sch Med, Div Infect Dis, Stanford, CA 94305 USA
[5] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA
基金
美国国家卫生研究院;
关键词
GB-VIRUS-C; HEPATITIS-G VIRUS; C/HEPATITIS G VIRUS; HIV-1; INFECTION; BONE-MARROW; REPLICATION; ACTIVATION; VIREMIA; LIVER; COINFECTION;
D O I
10.1099/vir.0.063016-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 naive, 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 naive (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.
引用
收藏
页码:1307 / 1319
页数:13
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