TY - JOUR
T1 - GaHV-2 ICP22 protein is expressed from a bicistronic transcript regulated by three GaHV-2 microRNAs
AU - Boumart, Imane
AU - Figueroa, Thomas
AU - Dambrine, Ginette
AU - Muylkens, Benoît
AU - Pejaković, Srdan
AU - Rasschaert, Denis
AU - Dupuy, Catherine
N1 - Funding Information:
This work was supported by grants from the Ligue contre le Cancer Grand Ouest-Comités (18, 29, 35, 36 and 37). S. P. is a ‘Fonds Pour la formation à la recherche dans l’industrie et dans l’agriculture’ (FRIA) PhD fellow (Belgium). We thank ‘Campus Fance’ and ‘Le consulat de France au Maroc’ for having supported financialy Imane Boumart.
Publisher Copyright:
© 2018 The Authors.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/9
Y1 - 2018/9
N2 - Herpesviruses have a lifecycle consisting of successive lytic, latent and reactivation phases. Only three infected cell proteins (ICPs) have been described for the oncogenic Marek’s disease virus (or Gallid herpes virus 2, GaHV-2): ICP4, ICP22 and ICP27. We focus here on ICP22, confirming its cytoplasmic location and showing that ICP22 is expressed during productive phases of the lifecycle, via a bicistronic transcript encompassing the US10 gene. We also identified the unique promoter controlling ICP22 expression, and its core promoter, containing functional responsive elements including E-box, ETS-1 and GATA elements involved in ICP22 transactivation. ICP22 gene expression was weakly regulated by DNA methylation and activated by ICP4 or ICP27 proteins. We also investigated the function of GaHV-2 ICP22. We found that this protein repressed transcription from its own promoter and from those of IE ICP4 and ICP27, and the late gK promoter. Finally, we investigated posttranscriptional ICP22 regulation by GaHV-2 microRNAs. We found that mdv1-miR-M5-3p and -M1-5p downregulated ICP22 mRNA expression during latency, whereas, unexpectedly, mdv1-miR-M4-5p upregulated the expression of the protein ICP22, indicating a tight regulation of ICP22 expression by microRNAs.
AB - Herpesviruses have a lifecycle consisting of successive lytic, latent and reactivation phases. Only three infected cell proteins (ICPs) have been described for the oncogenic Marek’s disease virus (or Gallid herpes virus 2, GaHV-2): ICP4, ICP22 and ICP27. We focus here on ICP22, confirming its cytoplasmic location and showing that ICP22 is expressed during productive phases of the lifecycle, via a bicistronic transcript encompassing the US10 gene. We also identified the unique promoter controlling ICP22 expression, and its core promoter, containing functional responsive elements including E-box, ETS-1 and GATA elements involved in ICP22 transactivation. ICP22 gene expression was weakly regulated by DNA methylation and activated by ICP4 or ICP27 proteins. We also investigated the function of GaHV-2 ICP22. We found that this protein repressed transcription from its own promoter and from those of IE ICP4 and ICP27, and the late gK promoter. Finally, we investigated posttranscriptional ICP22 regulation by GaHV-2 microRNAs. We found that mdv1-miR-M5-3p and -M1-5p downregulated ICP22 mRNA expression during latency, whereas, unexpectedly, mdv1-miR-M4-5p upregulated the expression of the protein ICP22, indicating a tight regulation of ICP22 expression by microRNAs.
KW - transcription regulation
KW - GaHV-2
KW - microRNA
KW - alphaherpesvirus
KW - translation regulation
KW - ICP22
KW - MicroRNA
KW - Translation regulation
KW - Alphaherpesvirus
KW - Transcription regulation
UR - https://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001124
UR - http://www.scopus.com/inward/record.url?scp=85053015846&partnerID=8YFLogxK
U2 - 10.1099/jgv.0.001124
DO - 10.1099/jgv.0.001124
M3 - Article
SN - 0022-1317
VL - 99
SP - 1286
EP - 1300
JO - The Journal of general virology
JF - The Journal of general virology
IS - 9
M1 - 001124
ER -