Hahn and colleagues previously showed that of the major Hepatitis C virus (HCV) proteins, only one, the nucleocapsid core protein, can confer on a carrier virus the ability to evade the host animal's immune system. Because this finding might help explain the long-term viral persistence that makes hepatitis C intractable, this group has now screened for lymphocyte proteins that can interact specifically with the viral core protein. Here they show that gC1qR, a receptor for complement protein C1q, is one such binding partner for core protein, and they identify the domains required on each protein that allow for this interaction. C1q, the endogenous ligand for this receptor, is also known to suppress T cell function, although C1q and the HCV core protein bind distinct sites on the gC1qR. Kittlesen et al. confirm that purified core protein blocks T-cell proliferation in a cell culture assay. They also show that a blocking antibodies to the core protein or to gC1qR can abolish this effect, raising the question of why endogenous anti-core antibodies do not have a similar protective effect in infected individuals. Nonetheless, in light of the earlier finding that an active T-cell response to core protein correlates with suppression of HCV, the present work may open the door to developing immune or other therapies for chronic hepatitis C.
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Contact: John Ashkenas
scied@the-jci.org
206-221-5690
Journal of Clinical Investigation
12-Nov-2000