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Journal of Virology, August 2000, p. 7016-7023, Vol. 74, No. 15
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

Ann T. Hoge, Sara B. Hendrickson, and William H. Burns*

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 beta -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.

Journal of Virology, August 2000, p. 7016-7023, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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