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

Chia-Lin Chen; Jeffrey Y Huang; Chun-Hsiang Wang; Stanley M Tahara; Lin Zhou; Yasuteru Kondo; Joel Schechter; Lishan Su; Michael M C Lai; Takaji Wakita; François-Loïc Cosset; Jae U Jung; Keigo Machida

doi:10.1038/ncomms13882

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

Nat Commun. 2017 Jan 9:8:13882. doi: 10.1038/ncomms13882.

Authors

Affiliations

¹ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
² Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
³ Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, USA.
⁴ Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
⁵ Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
⁶ International Center for Infectiology Research, Team EVIR, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007 Lyon, France.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes / immunology
B-Lymphocytes / virology*
B7-2 Antigen / genetics*
B7-2 Antigen / immunology
Cell Line, Tumor
DEAD Box Protein 58 / antagonists & inhibitors
DEAD Box Protein 58 / genetics
DEAD Box Protein 58 / immunology
Gene Expression Regulation
Gene Library
HEK293 Cells
Hep G2 Cells
Hepacivirus / immunology*
Host-Pathogen Interactions*
Humans
Immunologic Memory
Interferon-Induced Helicase, IFIH1 / genetics
Interferon-Induced Helicase, IFIH1 / immunology
MicroRNAs / antagonists & inhibitors
MicroRNAs / genetics
MicroRNAs / immunology
Protein Binding
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Receptors, Immunologic
Signal Transduction
Viral Envelope Proteins / genetics*
Viral Envelope Proteins / immunology
Viral Tropism / immunology*
Virus Replication

Substances

B7-2 Antigen
MIRN122 microRNA, human
MicroRNAs
RNA, Small Interfering
Receptors, Immunologic
Viral Envelope Proteins
glycoprotein E2, Hepatitis C virus
RIGI protein, human
IFIH1 protein, human
DEAD Box Protein 58
Interferon-Induced Helicase, IFIH1

Abstract

Publication types

MeSH terms

Substances

Grants and funding