Deletion of the rat cytomegalovirus immediate-early 1 gene results in a virus capable of establishing latency, but with lower levels of acute virus replication and latency that compromise reactivation efficiency.

Abstract

The IE1 and IE2 proteins encoded by the major immediate-early (MIE) transcription unit of cytomegaloviruses are thought to play key roles in the switch between latent and lytic cycle infection. Whilst IE2 is essential for triggering the lytic cycle, the exact roles of IE1 have not been resolved. An MIE-exon 4 deleted rat cytomegalovirus ({Delta}IE1) failed to synthesize the IE1 protein and did not disperse promyelocytic leukemia bodies (PML) early post-infection, but it was still capable of normal replication in fibroblast cell culture. However, {Delta}IE1 had diminished ability to infect salivary glands persistently in vivo and to reactivate from spleen explant cultures ex vivo. Quantitation of viral genomes in spleens of infected animals revealed a reduced amount of {Delta}IE1 virus produced during acute infection, suggesting a role for IE1 as a regulator in establishing a chronic or persistent infection, rather than in more directly influencing the latency or reactivation processes.