Down-regulation of human leukocyte antigen class I and II and β2-microglobulin expression in human herpesvirus-7-infected cells

Human herpesvirus (HHV)-7 is a ubiquitous virus that infects > 90% of adults. We show that HHV-7 impairs beta(2)-microglobulin and human leukocyte antigen (HLA) class I and II expression in lymphoid cells in vitro. Accordingly, infected cells were more sensitive to peripheral blood natural cytotoxic activity than were uninfected cells. Analysis of beta(2)-microglobulin and HLA expression in biopsy specimens from human submandibular glands confirmed the ability of HHV-7 to modulate the expression of these antigens in vivo. We demonstrate that the down-modulation of HLA by HHV-7 is linked to viral replication and is not merely a consequence of the interaction of virions with the cell surface. Infected cells can therefore efficiently escape host immune pressure, which might explain the persistence of HHV-7-positive cells in several kinds of tumors and chronic infectious diseases.