Murine gammaherpesvirus 68 cyclin D homologue is required for efficient reactivation from latency.
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 (MHV68(cy-)). MHV68(cy-) 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 MHV68(cy-) show deficient growth of the MHV68(cy-) in an acute infection. Infection of SCID mice with virus mixtures also showed decreased MHV68(cy-) virus growth, indicating that the deficiency is not mediated by T or B cells. Although mice infected with mixtures containing 100 times as much MHV68(cy-) 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.
Hoge
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AT
Departments of Medicine and Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Hendrickson
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SB
Burns
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WH
D000818:Animals; D002478:Cells, Cultured; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006566:Herpesviridae Infections / Q000821:virology*; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation; D017735:Virus Latency
D016213:Cyclins; C118264:HHV8-Vcyc protein, Human herpesvirus 8; D014764:Viral Proteins