Down-regulation of surface major histocompatibility complex class I by guinea pig cytomegalovirus.
Live attenuated strains of human cytomegalovirus are under development as vaccines to prevent birth defects resulting from congenital infections. These strains encode four proteins that inhibit surface expression of MHC class I, presumably to evade cytotoxic T-cell recognition and, perhaps, attenuate induction of immunity. To initiate studies of the role of class I down-regulation on congenital infection and vaccine efficacy, the ability of guinea pig cytomegalovirus to down-regulate class I was examined. Surface class I was specifically down-regulated on infected cells up to 8-fold. Sensitivity to UV irradiation and insensitivity to a viral DNA synthesis inhibitor revealed that immediate early or early viral gene(s) are responsible. Identification of these genes will permit future experiments to evaluate the role of class I down-regulation in congenital cytomegalovirus disease and its impact on vaccine efficacy. These findings should be pertinent to understanding human cytomegalovirus disease and may help guide the design of candidate vaccines.
Lacayo
Juan
J
Departments of Microbiology & Immunology and Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, Virginia 23298-01632, USA.
Sato
Hiroshi
H
Department of Parasitology, Hirosaki University School of Medicine, Hirosaki, Japan.
Kamiya
Haruo
H
Department of Parasitology, Hirosaki University School of Medicine, Hirosaki, Japan.
McVoy
Michael A
MA
Departments of Microbiology & Immunology and Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, Virginia 23298-01632, USA.
D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015536:Down-Regulation; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000821:virology; D049452:Green Fluorescent Proteins; D006168:Guinea Pigs; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins