[en] Varicella-zoster virus (VZV) is an Alphaherpesvirus responsible for two human diseases: primary exposure to the virus results in chicken pox (varicella) and reactivation following a period of latency in dorsal lia gives rise to shingles (zoster). Interestingly, several transcripts corresponding to regulatory proteins present during the lytic cycle can be found in latently infected cells. The IE62 protein, component of the viral tegument, is a nuclear phosphoprotein. IE62 may play a crucial role in triggering and regulating the replicative cycle of VZV since it transactivates all classes of VZV genes and is able to repress or activate its own promoter. Moreover, IE62 acts in synergy with IE4, another important regulatory protein, to stimulate VZV gene promoters and IE62 is responsible for the translocation of IE4 from the cytoplasm to the nucleus. IE4 is expressed at very early times of the VZV productive cycle, Predominantly localized in the cytoplasm, IE4 activates several VZV genes, either alone or in synergy with IE62, as well as heterologous viral genes. At the molecular level, IE4 seems to act both transcriptionally and post-transcriptionally. Another major VZV protein is a 45 kDa phosphorylated protein, called IE63, which is abundantly expressed at the onset of the productive cycle. It is also defected during latency in humans and in a rat animal model an unexpected observation in Alphaherpesviruses. IE63 displays little direct effect on VZV gene promoters, it shows no inhibitory effect on the transactivating functions of IE62 but it represses the IE4 mediated activation. Studies conducted to define the mode of action of three VZV regulatory proteins playing crucial roles in the latency and reactivation of the am-rus mil not only lead to a better understanding of the virus pathogenesis but will probably help define novel therapeutic tools.
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