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.