Specific transcriptional and post-transcriptional regulation of the major immediate early ICP4 gene of GaHV-2 during the lytic, latent and reactivation phases

Autor: Perrine Rasschaert, Ginette Dambrine, Imane Boumart, S. Laurent, Isabelle Gennart, Denis Rasschaert, Benoît Muylkens
Přispěvatelé: Université Francois Rabelais [Tours], Veterinary Integrated Research Unit, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), Université de Namur [Namur] (UNamur), Département Santé Animale (DEPT SA), Institut National de la Recherche Agronomique (INRA), Ligue contre le Cancer Grand Ouest’ (France), ‘Fonds Européen de Développement Régional’ (FEDER) EXMIR (no. 2835-34204), ‘Région Centre-Val de Loire’ MIRES (no. 200900038264) ‘Fonds de la recherche Scientifique’ (FNRS, grant FRFC J.0165.13, Methyllatency in Marek’s Disease Virus) (Belgium).
Rok vydání: 2018
Předmět:
Zdroj: Journal of General Virology
Journal of General Virology, Microbiology Society, 2018, 99, pp.355-368. ⟨10.1099/jgv.0.001007⟩
ISSN: 1465-2099
0022-1317
DOI: 10.1099/jgv.0.001007
Popis: Two supplementary tables and four supplementary figures are available with the online version of this article; International audience; Transcriptional and post-transcriptional mechanisms are involved in the switch between the lytic, latent and reactivation phases of the viral cycle in herpesviruses. During the productive phases, herpesvirus gene expression is characterized by a temporally regulated cascade of immediate early (IE), early (E) and late (L) genes. In alphaherpesviruses, the major product of the IE ICP4 gene is a transcriptional regulator that initiates the cascade of gene expression that is essential for viral replication. In this study, we redefine the infected cell protein 4 (ICP4) gene of the oncogenic Marek's disease virus (MDV or gallid herpesvirus 2) as a 9438 nt gene ended with four alternative poly(A) signals and controlled by two alternative promoters containing essentially ubiquitous functional response elements (GC, TATA and CCAAT boxes). The distal promoter is associated with ICP4 gene expression during the lytic and the latent phases, whereas the proximal promoter is associated with the expression of this gene during the reactivation phase. Both promoters are regulated by DNA methylation during the viral cycle and are hypermethylated during latency. Transcript analyses showed ICP4 to consist of three exons and two introns, the alternative splicing of which is associated with five predicted nested ICP4ORFs. We show that the ICP4 gene is highly and specifically regulated by transcriptional and post-transcriptional mechanisms during the three phases of the GaHV-2 viral cycle, with a clear difference in expression between the lytic phase and reactivation from latency in our model.
Databáze: OpenAIRE