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

• Published in: Nature communications 2017-01, Vol.8 (1), p.13882-13882, Article 13882
• Main Authors: Chen, Chia-Lin, Huang, Jeffrey Y., Wang, Chun-Hsiang, Tahara, Stanley M, Zhou, Lin, Kondo, Yasuteru, Schechter, Joel, Su, Lishan, Lai, Michael M C., Wakita, Takaji, Cosset, François-Loïc, Jung, Jae U, Machida, Keigo
• Format: Article
• Language: English
• Subjects: 13; 38/77; 631/250/255/234/2513/1551; 631/326/596/1905; 64; 82; 82/1; B-Lymphocytes - immunology; B-Lymphocytes - virology; B7-2 Antigen - genetics; B7-2 Antigen - immunology; Bacteriology; Cell Line, Tumor; Cells; DEAD Box Protein 58 - antagonists & inhibitors; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - immunology; Gene Expression Regulation; Gene Library; Genomes; HEK293 Cells; Hep G2 Cells; Hepacivirus - immunology; Hepatitis C; Host-Pathogen Interactions; Humanities and Social Sciences; Humans; Immunologic Memory; Immunology; Infections; Interferon-Induced Helicase, IFIH1 - genetics; Interferon-Induced Helicase, IFIH1 - immunology; Kinases; Life Sciences; Liver; Lymphocytes; Microbiology and Parasitology; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - immunology; multidisciplinary; Mutation; Neurosciences; Protein Binding; Receptors, Immunologic; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Signal Transduction; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Tropism - immunology; Virology; Virus Replication; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13882

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. Infection of B cells by hepatitis C virus (HCV) is poorly understood, but is thought to result in lymphoproliferative disorders. Here, Chen et al . identify CD86 as co-receptor for lymphotropic HCV and show that HCV infection inhibits memory B-cell function.