A nonstructural viral protein expressed by a recombinant vaccinia virus protects against lethal cytomegalovirus infection.
The nonstructural immediate-early protein pp89 of murine cytomegalovirus (MCMV) is the first viral protein synthesized after infection and has a regulatory function in viral gene expression. Despite its localization in the nucleus of infected cells, pp89 is also the dominant antigen recognized by MCMV-specific cytolytic T lymphocytes. The recombinant vaccinia virus MCMV-ieI-VAC, which expresses pp89, was used to study the capacity of this protein to induce protective immunity in BALB/c mice. Vaccination with MCMV-ieI-VAC induced a long-lasting immunity that protected mice against challenge with a lethal dose of MCMV but did not prevent infection and morbidity. In vivo depletion of CD8+ T lymphocytes before challenge completely abrogated the protective immunity. CD8+ T lymphocytes derived from MCMV-ieI-VAC-primed donors and adoptively transferred into sublethally irradiated and MCMV-infected recipients were found to limit viral replication in host tissues, whereas CD4+ T lymphocytes and pp89-specific antiserum had no protective effect. The data demonstrate for the first time that a single nonstructural viral protein can confer protection against a lethal cytolytic infection and that this immunity is entirely mediated by the CD8+ subpopulation of T lymphocytes.
Jonjić
S
S
Federal Research Centre for Virus Diseases of Animals, Tübingen, Federal Republic of Germany.
del Val
M
M
Keil
G M
GM
Reddehase
M J
MJ
Koszinowski
U H
UH
D000818:Animals; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D006564:Herpesviridae / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000276:immunology* / Q000494:pharmacology
D014764:Viral Proteins