20962076
not annotated - annotated - LINNAEUS only
Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission.
Hepatitis C virus (HCV) can initiate infection by cell-free particle and cell-cell contact-dependent transmission. In this study we use a novel infectious coculture system to examine these alternative modes of infection. Cell-to-cell transmission is relatively resistant to anti-HCV glycoprotein monoclonal antibodies and polyclonal immunoglobulin isolated from infected individuals, providing an effective strategy for escaping host humoral immune responses. Chimeric viruses expressing the structural proteins representing the seven major HCV genotypes demonstrate neutralizing antibody-resistant cell-to-cell transmission. HCV entry is a multistep process involving numerous receptors. In this study we demonstrate that, in contrast to earlier reports, CD81 and the tight-junction components claudin-1 and occludin are all essential for both cell-free and cell-to-cell viral transmission. However, scavenger receptor BI (SR-BI) has a more prominent role in cell-to-cell transmission of the virus, with SR-BI-specific antibodies and small-molecule inhibitors showing preferential inhibition of this infection route. These observations highlight the importance of targeting host cell receptors, in particular SR-BI, to control viral infection and spread in the liver.
Ann file
T1 Species 32 49 hepatitis C virus
N1 Reference T1 Taxonomy:11103
T2 Species 97 100 HCV
N2 Reference T2 Taxonomy:11103
T3 Out-of-scope 357 360 HCV
N3 Reference T3 Taxonomy:11103
T4 Species 619 622 HCV
N4 Reference T4 Taxonomy:11103
T5 Species 704 707 HCV
N5 Reference T5 Taxonomy:11103
T6 Species 78 95 Hepatitis C virus
N6 Reference T6 Taxonomy:11103