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

Chia-Lin Chen (1) , Jeffrey Y. Huang (1) , Chun-Hsiang Wang (1) , Stanley M. Tahara (1) , Lin Zhou (1) , Yasuteru Kondo (1) , Joel Schechter (1) , Lishan Su (2) , Michael M. C. Lai (1, 3) , Takaji Wakita (4) , Cosset François-Loïc (5) , Jae U. Jung (1) , Keigo Machida (1)

1 Keck School of Medicine [Los Angeles]
2 Department of Biology - Carolina Center for Genome Sciences - School of Medicine, Lineberger Comprehensive Cancer Center
3 Academia Sinica
4 National Institute of Infectious Diseases [Tokyo]
5 EVIR - Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy

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.

Domaines: Immunologie; Bactériologie; Virologie

Chia-Lin Chen, Jeffrey Y. Huang, Chun-Hsiang Wang, Stanley M. Tahara, Lin Zhou, et al.. Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2. Nature Communications, 2017, 8, pp.13882. ⟨10.1038/ncomms13882⟩. ⟨hal-01911337⟩