Murine cytomegalovirus m02 gene family protects against natural killer cell-mediated immune surveillance.
The murine cytomegalovirus m02 gene family encodes putative type I membrane glycoproteins named m02 through m16. A subset of these genes were fused to an epitope tag and cloned into an expression vector. In transfected and murine cytomegalovirus-infected cells, m02, m04, m05, m06, m07, m09, m10, and m12 localized to cytoplasmic structures near the nucleus, whereas m08 and m13 localized to a filamentous structure surrounding the nucleus. Substitution mutants lacking the m02 gene (SMsubm02) or the entire m02 gene family (SMsubm02-16) grew like their wild-type parent in cultured cells. However, whereas SMsubm02 was as pathogenic as the wild-type virus, SMsubm02-16 was markedly less virulent. SMsubm02-16 produced less infectious virus in most organs compared to wild-type virus in BALB/c and C57BL/6J mice, but it replicated to wild-type levels in the organs of immunodeficient gamma(c)/Rag2 mice, lacking multiple cell types including natural killer cells, and in C57BL/6J mice depleted of natural killer cells. These results argue that one or more members of the m02 gene family antagonize natural killer cell-mediated immune surveillance.
Oliveira
Sofia A
SA
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Park
Se-Ho
SH
Lee
Peter
P
Bendelac
Albert
A
Shenk
Thomas E
TE
D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000821:virology; D005814:Genes, Viral / Q000235:genetics*; D006566:Herpesviridae Infections / Q000276:immunology / Q000401:mortality / Q000821:virology; D007157:Immunologic Surveillance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000235:genetics*; D018146:Muromegalovirus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D009154:Mutation / Q000235:genetics; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D014764:Viral Proteins