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.
The immediate-early 1 (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 (DeltaIE1) failed to synthesize the IE1 protein and did not disperse promyelocytic leukaemia bodies early post-infection, but was still capable of normal replication in fibroblast cell culture. However, DeltaIE1 had a diminished ability to infect salivary glands persistently in vivo and to reactivate from spleen explant cultures ex vivo. Quantification of viral genomes in spleens of infected animals revealed a reduced amount of DeltaIE1 virus produced during acute infection, suggesting a role for IE1 as a regulator in establishing a chronic or persistent infection, rather than in influencing the latency or reactivation processes more directly.
Sandford
Gordon R
GR
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Schumacher
Uwe
U
Ettinger
Jakob
J
Brune
Wolfram
W
Hayward
Gary S
GS
Burns
William H
WH
Voigt
Sebastian
S
D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics*; D005347:Fibroblasts / Q000821:virology; D006566:Herpesviridae Infections / Q000821:virology; D017874:Immediate-Early Proteins / Q000235:genetics*; D066298:In Vitro Techniques; D018146:Muromegalovirus / Q000235:genetics / Q000502:physiology*; D051381:Rats; D012469:Salivary Glands / Q000821:virology; D017384:Sequence Deletion; D013154:Spleen / Q000821:virology; D015534:Trans-Activators / Q000235:genetics*; D014774:Virulence; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
D004279:DNA, Viral; C088645:IE1 protein, cytomegalovirus; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D015534:Trans-Activators