REGULATION OF THE INFECTIOUS CYCLES OF TH E VARICELLA-ZOSTER VIRUS

Varicella-zoster virus (VZV) is an Alphaherpesvirus responsible for tw o 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 transcript s corresponding to regulatory proteins present during the lytic cycle can be found in latently infected cells. The IE62 protein, component o f the viral tegument, is a nuclear phosphoprotein. IE62 may play a cru cial role in triggering and regulating the replicative cycle of VZV si nce 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 cytopla sm to the nucleus. IE4 is expressed at very early times of the VZV pro ductive cycle, Predominantly localized in the cytoplasm, IE4 activates several VZV genes, either alone or in synergy with IE62, as well as h eterologous viral genes. At the molecular level, IE4 seems to act both transcriptionally and post-transcriptionally. Another major VZV prote in is a 45 kDa phosphorylated protein, called IE63, which is abundantl y expressed at the onset of the productive cycle. It is also defected during latency in humans and in a rat animal model an unexpected obser vation in Alphaherpesviruses. IE63 displays little direct effect on VZ V gene promoters, it shows no inhibitory effect on the transactivating functions of IE62 but it represses the IE4 mediated activation. Studi es conducted to define the mode of action of three VZV regulatory prot eins playing crucial roles in the latency and reactivation of the am-r us mil not only lead to a better understanding of the virus pathogenes is but will probably help define novel therapeutic tools.