Expression of adenovirus E3/19K protein does not alter mouse MHC class I-restricted responses to vaccinia virus.
The adenovirus E3/19K glycoprotein forms a tight complex with most human and certain mouse MHC class I allomorphs, retaining them in the endoplasmic reticulum by virtue of its cytosolic carboxyl terminal amino acids. This prevents the presentation of viral antigens at the cell surface to class I-restricted cytotoxic T lymphocytes (CTL). In adenovirus infection of cotton rats, E3/19K appears to act as an anti-inflammatory and/or immunosuppressive factor. Further studies of the role of E3/19K in adenovirus pathogenesis have been hampered by the lack of sufficient knowledge concerning the immune system of the cotton rat and by the poor correlation between adenovirus infection in mice and humans. We therefore addressed the function of this adenovirus glycoprotein in virus pathogenesis by infecting B10.HTG (H-2KdDb) mice with a vaccinia virus (VV) recombinant encoding E3/19K. The Kd and Db allomorphs normally present VV antigens to CTL and have high affinity for E3/19K. Infected mice were examined for the kinetics of virus replication in various tissues and the generation of natural killer (NK) cell and CTL responses. It was found that expression of E3/19K by vaccinia virus had no detectable effect on CTL responses, NK responses, or viral replication. These findings suggest that immune modulating proteins evolve to exploit unique circumstances of the host immune response to a given virus.
Cox
J H
JH
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Buller
R M
RM
Bennink
J R
JR
Yewdell
J W
JW
Karupiah
G
G
D017503:Adenovirus E3 Proteins / Q000502:physiology*; D000818:Animals; D006183:H-2 Antigens / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
D017503:Adenovirus E3 Proteins; D006183:H-2 Antigens