Neither the cellular binding sites nor the extrahepatic reservoirs for the hepatitis C virus (HCV) are well understood. The study of Hamaia and colleagues (page 2293) investigates the characteristics of HCV binding to platelets and 2 mononuclear cell lines. Among the interesting findings of this study: (1) Most HCV (95%) circulates bound to IgG; only 1% of circulating virus is cell bound. (2) HCV binds efficiently to platelets. (3) The mechanism of HCV binding to platelets is different than to mononuclear cells in that platelets bind free and complexed HCV equally well and that platelet binding does not reach a saturation limit; platelet binding may represent simple absorption. (4) Although CD81 has been proposed as a major receptor for HCV binding, HCV binds equally to CD81+ cells (MOLT-4) and CD81− cells (U-937 and platelets) and antibody to CD81 does not block HCV binding. Thus, CD81-independent binding sites must exist. (5) The hypervariable region 1 (HVR1) of HCV appears to play an important role in viral attachment. (6) The binding characteristics of recombinant HCV envelope (rE2) are different than those of native HCV, suggesting that studies that employ rE2 may not be fully representative of natural infection.
The implications of this study are that platelets as well as mononuclear cells may serve to transport HCV to sites of immune recognition or alternately to sequester virions from such recognition. In addition, these hematologic cells may serve as important reservoirs of HCV that account for the almost universal infection of HCV-naive livers following liver transplantation. This study also indicates that HCV binding is not dependent on the postulated HCV receptor, CD81, and that HVR1 serves as an important attachment site of the virion. HVR1 is also the region presumed to be the target for neutralizing antibody against HCV and the region that under immune pressure mutates to create the vast HCV quasi species.
