Adenovirus type 5 E3 gene products interfere with the expression of the cytolytic T cell immunodominant E1a antigen.
Effects of mutations in the adenovirus 5 (Ad 5) E3 transcription unit on the immune Tc cell response to Ad 5 were investigated. We observed enhanced lysis of L929 target cells infected with the E3 defective mutant viruses dl 327 and dl 355 compared to wild-type (wt) Ad 5 by Ad 5 immune Tc cells. This enhanced lysability was not due to E3 effects on the cell surface expression of class I MHC H-2Kk molecules as determined by monoclonal antibody binding or alloreactive Tc cell recognition. Furthermore MHC class I molecules were able to efficiently present vaccinia virus antigens in the presence of the Ad 5 E3 genes, excluding functional modification of class I MHC antigens by E3 gene products. When levels of the Ad 5 immunodominant antigen E1a were compared between wt and E3 mutant viruses, we observed an 8- to 10-fold increase in E1a levels in E3 mutant-infected cells over wt Ad 5-infected cells. No differences were observed between these viruses at the mRNA level. We conclude that E3 products interfere with Ad 5 immune Tc cell responses by some post-transcriptional mechanism which reduces expression of the E1a immunodominant antigen.
Zhang
X L
XL
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberta, ACT.
Bellett
A J
AJ
Hla
R T
RT
Braithwaite
A W
AW
Müllbacher
A
A
D017456:Adenovirus Early Proteins; D000261:Adenoviruses, Simian / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005814:Genes, Viral; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics; D014616:Vaccinia virus / Q000276:immunology; D014764:Viral Proteins
D017456:Adenovirus Early Proteins; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D016056:Immunodominant Epitopes; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins