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Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: Implications of HCV lymphotropism
被引:117
作者:
Pal, S
Sullivan, DG
Kim, S
Lai, KKY
Kae, J
Cotler, SJ
Carithers, RL
Wood, BL
Perkins, JD
Gretch, DR
机构:
[1] Univ Washington, Med Ctr, Seattle, WA 98195 USA
[2] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA
[3] Rush Presbyterian St Lukes Med Ctr, Sect Hepatol, Chicago, IL 60612 USA
[4] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA
[5] Univ Washington, Med Ctr, Dept Surg, Seattle, WA 98195 USA
关键词:
D O I:
10.1053/j.gastro.2005.12.039
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
Background & Aims: The pathogenesis of chronic hepatitis C is poorly understood. This study examines the ability of hepatitis C virus (HCV) to infect, replicate in, and produce progeny virus from perihepatic lymph nodes in vivo. Methods: Lymph node (LN) biopsy specimens were taken from 20 patients with HCV genotype 1. infection and end-stage liver disease and 20 noninfected negative controls. Sections were probed with HCV RNA strand-specific riboprobes and antibodies specific for HCV core and nonstructural region 3 antigens plus B-cell (CD20) and T-cell (CD2) antigens. In a selected case, HCV quasispecies in serum, peripheral blood mononuclear cells, liver, and perihepatic lymph nodes were analyzed by clonal frequency analysis and sequencing. Results: HCV infection was confirmed in 17 of 20 (85%) of lymph node specimens by in situ hybridization, and HCV replication was confirmed in 50% of cases by detection of HCV replicative intermediate RNA. HCV core and nonstructural 3 antigens were detected in lymph nodes by immunocytochemistry. Infected cell phenotypes were primarily CD20 B cells, although other cell types were positive for HCV replication markers. Quasispecies analysis in one case indicated that 68% of variants circulating in serum were also present in lymphoid tissues, and only 40% of serum variants were identified in liver, documenting a major contribution of lymphoid replication to HCV viremia. Conclusions: HCV lymphotropism provides new insights into the complex pathobiology of chronic hepatitis C in humans. We demonstrate for the first time a major contribution of extrahepatic HCV replication to circulating virus in serum (viremia).
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页码:1107 / 1116
页数:10
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