Herpesvirus Saimiri open reading frame 50 (Rta) protein reactivates the lytic replication cycle in a persistently infected A549 cell line

Herpesviruses occur in two distinct forms of infection, lytic replication a nd latent persistence. In this study, we investigated the molecular mechani sms that govern the latent-lytic switch in the prototype gamma-2 herpesviru s, herpesvirus saimiri (HVS). We utilized a persistently HVS-infected A549 cell line, in which HVS DNA is stably maintained as nonintegrated circular episomes, to assess the role of the open reading frame 50 (ORF 50) (Rta) pr oteins in the latent-lytic switch. Northern blot analysis and virus recover y assays determined that the ORF 50a gene product, when expressed under the control of a constitutively active promoter, was sufficient to reactivate the entire lytic replication cycle, producing infectious virus particles. F urthermore, although the ORF 50 proteins of HVS strains A11 and C488 are st ructurally divergent, they were both capable of inducing the lytic replicat ion cycle in this model of HVS latency.