title: Varicella-zoster virus ORF47 protein kinase, which is required for replication in human T cells, and ORF66 protein kinase, which is expressed during latency, are dispensable for establishment of latency.
abstract: Varicella-zoster virus (VZV) results in a lifelong latent infection in human sensory and cranial nerve ganglia after primary infection. VZV open reading frame 47 (ORF47) and ORF66 encode protein kinases that phosphorylate several viral proteins, including VZV glycoprotein gE and ORF32, ORF62, and ORF63 proteins. Here we show that the ORF47 protein kinase also phosphorylates gI. While ORF47 is essential for virus replication in human T cells and skin, we found the gene to be dispensable for establishment of latent infection in dorsal root ganglia of rodents. ORF66 protein is expressed during latency. Rodents infected with VZV unable to express ORF66 developed latent infection at a rate similar to that for the parental virus. ORF63 transcripts, a hallmark of VZV latency, were also detected in similar numbers of animals infected with the ORF47 and ORF66 mutants and with the parental virus. VZV mutants unable to express four of the six genes that do not have herpes simplex virus (HSV) homologs (ORFs 1, 13, 32, 57) were also unimpaired for establishment of latency. While a truncated HSV VP16 mutant was previously reported to be unable to establish latency in a mouse model, we found that VZV with a deletion of ORF10, the homolog of HSV VP16, was dispensable for establishment of latency. Thus, seven genes, including one expressed during latency, are dispensable for establishing latent VZV infection.
mesh_terms: D000818:Animals; D005260:Female; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology*; D016205:Sigmodontinae; D013601:T-Lymphocytes / Q000821:virology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000502:physiology*; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins; D014764:Viral Proteins; C056913:glycoprotein E, varicella-zoster virus; D011494:Protein Kinases; C085818:Varicella-Zoster ORF47-associated protein kinase