Inhibition of apoptosis in BHV-1-infected cells depends on Us3 serine/threonine kinase and its enzymatic activity

Agnieszka Brzozowska , Andrea Lipińska , Natalia Derewońko , Dorota Lesiak , Michał Rychłowski , Łukasz Rąbalski , Krystyna Bieńkowska Szewczyk

Abstract

Us3 protein is a serine/threonine kinase conserved within the Alphaherpesvirinae subfamily of herpesviruses. The Us3 homologs of herpes simplex virus, pseudorabies virus, and bovine herpesvirus type 5 have been shown to block apoptosis triggered by viral infection or exogenous inducers. To determine whether these characteristics are shared by bovine herpesvirus type 1 Us3, we constructed two viral mutants: BHV-1 Us3 deletion mutant (BHV-1ΔUs3) and a kinase-dead mutant (BHV-1KD). Flow cytometry analysis and TUNEL assay clearly demonstrated, that only BHV-1 wild type virus suppressed infection-induced apoptosis and protected cells from apoptosis triggered by exogenous factors: sorbitol or staurosporine. Us3 of BHV-1 was directly capable of blocking apoptosis without the presence of other viral proteins. The presence of Us3 correlated with phosphorylation of BAD, a pro-apoptotic Bcl-2 family member. Our results clearly indicate that BHV-1 Us3 is necessary for efficient blocking of apoptosis triggered by viral infection and exogenous factors.
Author Agnieszka Brzozowska ZBMW
Agnieszka Brzozowska,,
- Laboratory of Virus Molecular Biology
, Andrea Lipińska ZBMW
Andrea Lipińska,,
- Laboratory of Virus Molecular Biology
, Natalia Derewońko MWB UG i GUMed
Natalia Derewońko,,
- Intercollegiate Faculty of Biotechnology UG
, Dorota Lesiak ZBMW
Dorota Lesiak,,
- Laboratory of Virus Molecular Biology
, Michał Rychłowski ZBMW
Michał Rychłowski,,
- Laboratory of Virus Molecular Biology
, Łukasz Rąbalski ZSzR
Łukasz Rąbalski,,
- Laboratory of Recombinant Vaccines
, Krystyna Bieńkowska Szewczyk ZBMW
Krystyna Bieńkowska Szewczyk,,
- Laboratory of Virus Molecular Biology
Journal seriesVirology, ISSN 0042-6822
Issue year2018
Vol513
Pages136-145
Publication size in sheets0.5
Keywords in EnglishUs3 serine/threonine kinase, alphaherpesviruses, BHV-1, apoptosis
DOIDOI:10.1016/j.virol.2017.09.029
URL https://doi.org/10.1016/j.virol.2017.09.029
Languageen angielski
Score (nominal)30
ScoreMinisterial score = 25.0, 09-02-2018, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 09-02-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.353 (2) - 2016=3.164 (5)
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