Figure 5. Proposed model for viral cyclin requirements in virus infection.

Recombinant knock-in viruses with various viral or mammalian cyclins expressed from the endogenous gHV68 viral cyclin locus are depicted at upper left. Genetic complementation analysis of this panel of viruses demonstrated that the viral cyclins of gHV68 and of KSHV are functionally conserved and are unique in their ability to support all cyclin-dependent aspects of infection, depicted as three different panels. Further, mammalian cyclins able to function in virus infection comprised two genetically distinct groups, based on their ability to complement either persistent infection in endothelial cells (lower left) or reactivation from latency in lymphocytes (lower right). Finally, we propose that the unique capacity of the viral cyclins to support acute virus production and lethal pneumonia in the lungs of immune deficient mice does not reflect another distinct genetic requirement of viral cyclins. Rather, we hypothesize that both persistent infection and reactivation from latency contribute to optimal acute virus production in the lungs (upper right), as indicated by the combination of blue and yellow.