Hepatitis C virus lymphotrophism: lessons from a decade of studies

The possibility that HCV infects lymphoid cells has been widely discussed. Evidence in favor of HCV tropism for lymphoid cells derives from a series of data including: (1) the higher sensitivity of testing HCVRNA in PBMC than in serum or plasma samples, with possible detection of HCV RNA-positive PBMC in the absence of HCV viremia; (2) short-term cultures of PBMC which yield a significant increase in the amount of viral RNA on stimulation by mitogens; (3) results of "in situ" methods (i.e. in situ hybridization, immunofluorescence); (4) efficient infection of lymphoid cell lines or PBMC from normal individuals; (5) the persistence of HCV RNA in PBMC obtained from HCV-positive subjects and injected into SCID mice; (6) the long-term persistence of HCV RNA in PBMC in spite of HCV RNA negativity of serum and liver in sustained responder patients after therapy. The principal criticisms concerning effective HCV infection of lymphoid cells arise from technical difficulty in identifying HCV RNA replicative intermediate in these elements. Conflicting data may also result from differences in PBMC infection by different genotypes, samples taken at different stages in the disease process and differences in the sensitivity of detection methods, as well as low replication levels and/or proportion of infected PBMC. Interesting available data about HCV lymphotropism, which is possibly important in influencing the natural history of infection, include: (1) possible preferential viral tropism for specific PBMC subsets; (2) different lymphotropism of different viral strains; (3) selection of distinctive viral strains; (4) identification of putative HCV cell receptors; (5) association between determination of HCV lymphatic infection and t(14; 18) translocation. The clinical correlates of HCV lymphotropism are potentially very numerous, including, first, its role in determining HCV-related lymphoproliferative disorders.