Modulation of HLA-G Antigens Expression by Human Cytomegalovirus: Specific Induction in Activated Macrophages Harboring Human Cytomegalovirus Infection

Abstract

After infection, human CMV (HCMV) establishes a latent and persistent infection in immature myeloid progenitors and peripheral blood monocytes. Completion of the HCMV life cycle is possible upon maturation of monocytes to tissue macrophages and under permissive circumstances, e.g., immunosuppression. We investigated the hypothesis that HLA-G molecules could be induced during HCMV reactivation in activated macrophages to favor virus dissemination. In this study, we provide evidence that HLA-G Ags are produced during viral reactivation in macrophages generated after allogeneic stimulation of HCMV latently infected monocytes. While HLA-G surface expression is up-regulated, 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 between HLA-G Ag induction and HCMV infection was confirmed in U-373 MG astrocytoma cells. Soluble HLA-G expression is stimulated upon HCMV infection, and this modulation depends on the cooperative action of the two immediate-early-1 pp72 and immediate-early-2 pp86 products. Because HLA-G transcription is active in macrophages and U-373 MG astrocytoma cells, it is likely that the modulation of HLA-G protein expression during HCMV replication occurs at a post-transcriptional level. Our data suggest that induction of HLA-G molecules could be an additional mechanism that helps HCMV to subvert host defenses.

Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G

“…Our finding that ILT2 and ILT4 bind with a higher affinity to HLA-G than to classical MHCIs raises the possibility that both the ILTs may contribute to functional interactions between leukocytes expressing ILTs (T, NK, and myelomonocytic cells) and cells expressing HLA-G. The latter include thymic epithelial cells, fetal trophoblast tissue, some cancers, and the cells infected by human cytomegalovirus (37).…”

A Specific Interferon (IFN)-stimulated Response Element of the Distal HLA-G Promoter Binds IFN-regulatory Factor 1 and Mediates Enhancement of This Nonclassical Class I Gene by IFN-β

“…Complementary DNAs were prepared from total RNA using oligo(dT) [12][13][14][15][16][17][18] primers and Moloney murine leukemia virus reverse transcriptase (Life Technologies, Inc.). PCR amplification of the cDNA preparation was carried out in a thermal cycler (PerkinElmer Life Sciences, Norwalk, CT).…”

Modulation of HLA-G and HLA-E Expression in Human Neuronal Cells After Rabies Virus or Herpes Virus Simplex Type 1 Infections

“…One such molecule, the Ligand of Fas, FasL, has been shown to be involved in the killing of migratory T cells into the nervous system (NS) in rabies virus (RABV) infection [2,3]. HLA-G, a non classical MHC molecule which expression in cells is up regulated following infection with human cytomegalovirus (HCMV), human immunodeficiency virus (HIV-1) and RABV could also contribute by a similar mechanism to the immunoevasion of these viruses [4][5][6][7][8]. In addition, HIV-1 and HCMV up regulate the expression of another non classical MHC class I molecule,…”