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Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.

ABSTRACT: B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells. By cDNA library screening, we identified an immune cell-specific, co-stimulatory receptor B7.2 (CD86) as a co-receptor of lymphotropic HCV. Infection of B cells by HCV inhibited the recall reaction to antigen stimulation. Together, a co-receptor B7.2 enabled lymphotropic HCV to infect memory B cells, leading to inhibition of memory B-cell function and persistent HCV infection in HCV-infected hosts.

SUBMITTER: Chen CL

PROVIDER: S-EPMC5227552 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.

Chen Chia-Lin CL Huang Jeffrey Y JY Wang Chun-Hsiang CH Tahara Stanley M SM Zhou Lin L Kondo Yasuteru Y Schechter Joel J Su Lishan L Lai Michael M C MM Wakita Takaji T Cosset François-Loïc FL Jung Jae U JU Machida Keigo K

Nature communications 20170109

B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, R ...[more]

PMID: 28067225

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Project description:BackgroundHepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection.MethodsDemographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA.ResultsA total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P < 0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0-5.57] versus 5.87[IQR, 3.54-6.71] Log10 IU/mL, respectively; P < 0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P < 0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3-3.43] versus 3.06[IQR, 2-4.28] Log10 IU/mL, respectively; P < 0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group.ConclusionThese results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection.

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Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.

Publications

Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.

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