title: Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class I expression in cells from human and macaque hosts.
abstract: B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8(+) T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are representative of foreign and natural host initial target cells of B virus. Our results show <20% downregulation of surface MHC class I molecules in either type of host cells infected with B virus, which is statistically insignificantly different from that observed in uninfected cells. We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA-G, involved in NK cell inhibition. Our results showed significant upregulation of HLA-E and HLA-G in host cells infected with B virus relative to the amounts observed in other herpesvirus-infected cells. These results suggest that B virus-infected cell surfaces maintain normal levels of MHC class Ia molecules, a finding unique among simplex viruses. This is a unique divergence in immune evasion for B virus, which, unlike human simplex viruses, does not inhibit the transport of peptides for loading onto MHC class Ia molecules because B virus ICP47 lacks a transporter-associated protein binding domain. The fact that MHC class Ib molecules were significantly upregulated has additional implications for host-pathogen interactions.
authors.affiliation: Viral Immunology Center, Department of Biology, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Mugdha
authors.initials: M
authors.lastname: Vasireddi
authors.forename: Julia
authors.initials: J
authors.lastname: Hilliard
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D059951:HLA-G Antigens / Q000378:metabolism; D006568:Herpesvirus 1, Cercopithecine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D000097625:HLA-E Antigens
chemical_list: D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens