Human cytomegalovirus tegument protein pp71 directs long-term gene expression from quiescent herpes simplex virus genomes.
The human cytomegalovirus tegument protein pp71 is important for transactivation of immediate-early (IE) gene expression and for the efficient initiation of virus replication. We have analyzed the properties of pp71 by assaying its effects on gene expression from the genome of in1312, a herpes simplex virus type 1 (HSV-1) mutant devoid of functional VP16, ICP0, and ICP4. Upon infection of human fibroblasts, in1312-derived viruses are repressed and retained in a quiescent state, but the presence of pp71 prevented the quiescent state from being attained. Reporter gene cassettes cloned into the in1312 genome, in addition to the endogenous IE promoters, remained active for at least 12 days postinfection, and infected cells were viable and morphologically normal. Cells expressing pp71 remained responsive to the HSV-1 transactivating factors VP16 and ICP4 and to trichostatin A. The C-terminal 61 amino acids, but not the LACSD motif, were required for pp71 activity. In addition to preventing attainment of quiescence, pp71 was able to disrupt the quiescent state of in1312 derivatives and promote the resumption of viral gene expression after a lag of approximately 3 days. The results extend the functional analysis of pp71 and suggest a degree of similarity with the HSV-1 IE protein ICP0. The ability to provoke slow reactivation of quiescent genomes, in conjunction with cell survival, represents a novel property for a viral structural protein.
Preston
Chris M
CM
Medical Research Council Virology Unit, Glasgow, Scotland, United Kingdom. c.preston@vir.gla.ac.uk
Nicholl
Mary Jane
MJ
D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011995:Recombination, Genetic; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation; D017735:Virus Latency
D017405:Herpes Simplex Virus Protein Vmw65; D017874:Immediate-Early Proteins; D014764:Viral Proteins; C048925:herpes simplex virus, type 1 protein ICP4; C051298:cytomegalovirus phosphoprotein 71kDa; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1