- Adaptation of hepatitis C virus to mouse CD81 permits
infection of mouse cells in the absence of human entry factors
(2010) - Hepatitis C virus (HCV) naturally infects only humans
and chimpanzees. The determinants responsible for this narrow
species tropism are not well defined. Virus cell entry involves
human scavenger receptor class B type I (SR-BI), CD81, claudin-1
and occludin. Among these, at least CD81 and occludin are
utilized in a highly species-specific fashion, thus contributing
to the narrow host range of HCV. We adapted HCV to mouse CD81
and identified three envelope glycoprotein mutations which
together enhance infection of cells with mouse or other rodent
receptors approximately 100-fold. These mutations enhanced
interaction with human CD81 and increased exposure of the
binding site for CD81 on the surface of virus particles. These
changes were accompanied by augmented susceptibility of adapted
HCV to neutralization by E2-specific antibodies indicative of
major conformational changes of virus-