HCV and Blood Cells: How Can We Distinguish Infection from Association?

The liver is the primary target of hepatitis C virus (HCV) infection. However, HCV RNA and protein are often observed to associate with B cells and other blood cells. Are these cells truly infected, and if so, does the infection lead to B cell abnormalities? Not all investigators agree. This chapter discusses our recommendations for a rigorous evaluation of the potential roles of blood cells as sites of HCV infection. The detection of HCV RNA and protein should be combined with evaluations of whether levels of these markers are sensitive to potent antiviral compounds that block HCV infection in liver cells. RNA quantitation should include documentation of sensitivity and specificity as well as a number of critical controls. Similarly, reports of protein detection should include documentation of the specificity of the antibodies used, and particularly of the frequency of antigen-positive cells relative to the number of HCV genomes detected. B cells, like other blood cells, do not express all of the cellular factors believed to be required for HCV entry or productive infection. Thus, a number of significant questions must be addressed before we understand whether, and how, infection of B cells contributes to the pathogenesis of mixed cryoglobulinemia.