La régulation des cycles infectieux du virus de la varicelle et du zona.

Abstract

Le virus de la varicelle et du zona (VZV) est responsable de ces deux syndromes cliniques distincts. Pendant la periode d' incubation de la varicelle, le virus se multiplie au niveau de divers organes. Il peut ensuite gagner le systeme nerveux peripherique et y rester latent pendant une periode variable, avant d' etre reactive sous la forme du zona. Trois proteines virales ont ete mises en cause dans cette reactivation du virus: la phosphoproteine nucleaire virale IE62, synthetisee durant la phase precoce immediate (IE) du cycle et qui active l' expression de toutes les classes de genes viraux ; la proteine IE4, principalement cytoplasmique, qui agit en synergie avec IE62 pour activer des promoteurs des genes du VZV; la phosphoproteine IE63, seule a etre abondamment synthetisee pendant la latence dans les neurones des ganglions sensoriels, qui semble constituer une cible pour le systeme immunitaire. Sa presence lors d' une infection productive mais egalement pendant la latence est un cas unique parmi les Alphaherpesvirus et suggere qu' elle pourrait jouer un role dans l' etablissement et le controle de la latence.

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 root ganglia 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 detected 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 virus will not only lead to a better understanding of the virus pathogenesis but will probably help define novel therapeutic tools. [References: 34]