Modulation of HLA-G antigens expression by human cytomegalovirus: Specificinduction in activated macrophages harboring human cytomegalovirus infection

After infection, human CMV (HCMV) establishes a latent and persistent infec tion in immature myeloid progenitors and peripheral blood monocytes, Comple tion of the HCMV life cycle is possible upon maturation of monocytes to tis sue macrophages and under permissive circumstances, e.g., immunosuppression . We investigated the hypothesis that HLA-G molecules could be induced duri ng HCMV reactivation in activated macrophages to favor virus dissemination. In this study, we provide evidence that HLA-G Ags are produced during vira l reactivation in macrophages generated after allogeneic stimulation of HCM V latently infected monocytes. While HLA-G surface expression Is up-regulat ed, classical MHC-I molecules are partially down-regulated by HCMV. In vivo , bronchoalveolar macrophages collected from patients suffering from acute HCMV pneumonitis also express HLA-G molecules. The direct correlation betwe en HLA-G Ag induction and HCMV infection was confirmed in U-373 MG astrocyt oma cells. Soluble HLA-G expression is stimulated upon HCMV infection, and this modulation depends on the cooperative action of the two immediate-earl y-1 pp72 and immediate-early-2 pp86 products. Because HLA-G transcription i s active in macrophages and U-373 MG astrocytoma cells, it is likely that t he modulation of HLA-G protein expression during HCMV replication occurs at a post-transcriptional level. Our data suggest that induction of HLA-G mol ecules could be an additional mechanism that helps HCMV to subvert host def enses.