Disease relevance of ORF63

• The live attenuated varicella vaccine virus exhibited the same pattern of short-term replication, persistence of viral DNA, and prominent ORF63 transcription as the clinical isolates [1].
• The immediate-early 63-kDa (IE63) protein of varicella-zoster virus (VZV) is a phosphoprotein encoded by open reading frame (ORF) ORF63/ORF70 [2].
• The IR4 ORF exhibits significant homology to the immediate-early gene US1 (ICP22) of herpes simplex virus type 1 and to the ICP22 homologs of varicella-zoster virus (ORF63), pseudorabies virus (RSp40), and equine herpesvirus 4 (ORF4) [3].
• The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51) [4].
• An EHV-1 mutant, Ab4-GFP, was constructed by inserting a green fluorescent protein (GFP) expression cassette flanked by lox P at both ends into the intergenic region between ORF 62 and ORF 63 [5].

High impact information on ORF63

• The effect of each of these mutations implies that the intact binding site sequence regulates native ORF62 and ORF63 transcription [6].
• In summary, most mutations of ORF63 made with our VZV cosmid system were lethal for infectivity [2].
• Thus, ORF63 is not required for VZV to enter ganglia but is the first VZV gene shown to be critical for establishment of latency [7].
• We have deleted >90% of both copies of the ORF63 gene from the VZV genome [7].
• Examination of dorsal root ganglia 3 days after infection showed high levels of VZV DNA in animals infected with either ORF63 mutant or parental virus; however, by days 6 and 10 after infection, the level of viral DNA in animals infected with the ORF63 mutant was significantly lower than that in animals infected with parental virus [7].

Biological context of ORF63

• To identify functional domains, 22 ORF63 mutations were evaluated for effects on IE63 binding to the major VZV transactivator, IE62, and on IE63 phosphorylation and nuclear localization in transient transfections, and after insertion into the viral genome with VZV cosmids [2].
• Nucleotide sequences of the intergenic region between ORF 62 and ORF 63 of equine herpesvirus 1 (EHV-1) isolates were analyzed [5].

Anatomical context of ORF63

• The reporter viruses were used to evaluate ORF62 and ORF63 transcription during VZV replication in cultured fibroblasts and in skin xenografts in SCIDhu mice in vivo [6].

Associations of ORF63 with chemical compounds

• The ORF47 kinase phosphorylated maltose-binding protein, the mouse IgG2A heavy chain, the rabbit IgG heavy chain, casein, VZV ORF62, and VZV ORF63 [8].

Physical interactions of ORF63

• This requirement may be related to our observation that ORF63 interacts directly with ORF62, the major immediate-early transactivating protein of VZV [9].

Other interactions of ORF63

• 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 [10].

References