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Journal of Virology, August 2000, p. 7016-7023, Vol. 74, No. 15
Departments of Medicine and Microbiology and
Molecular Genetics, Medical College of Wisconsin, Milwaukee,
Wisconsin 53226
Received 1 March 2000/Accepted 12 May 2000
Murine gammaherpesvirus 68 (MHV68) is a gammaherpesvirus that was
first isolated from murid rodents. MHV68 establishes a latent infection in the spleen and other lymphoid organs. Several
gammaherpesviruses, including herpesvirus saimiri, human herpesvirus 8, and MHV68, encode proteins with extensive homology to the D-type
cyclins. To study the function of the cyclin homologue, a recombinant
MHV68 has been constructed that lacks the cyclin homologue and
expresses
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Murine Gammaherpesvirus 68 Cyclin D Homologue Is
Required for Efficient Reactivation from Latency
-galactosidase as a marker (MHV68cy
).
MHV68cy
grows in vitro with kinetics and to titers
similar to those of the wild type. BALB/c mice infected with
mixtures of equivalent amounts of the wild type and
MHV68cy
show deficient growth of the
MHV68cy
in an acute infection. Infection of SCID
mice with virus mixtures also showed decreased MHV68cy
virus growth, indicating that the deficiency is not mediated by T or B
cells. Although mice infected with mixtures containing 100 times as
much MHV68cy
had greater splenic titers of the mutant
virus than wild-type virus in acute infection, at 28 days
postinfection splenocytes from these mice reactivated primarily
wild-type virus. Quantitative PCR data indicate that equivalent genomes
were present in the latent state. Reinsertion of the cyclin homologue
into the cyclin-deleted virus restored the wild-type
phenotype. These results indicate that the MHV68 cyclin D
homologue mediates important functions in the acute infection and
is required for efficient reactivation from latency.
*
Corresponding author. Mailing address: Departments of
Medicine and Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226. Phone: (414) 456-4989. Fax: (414) 456-6533. E-mail: wburns{at}mcw.edu.
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