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The SAT protein of porcine parvovirus accelerates viral spreading through irreversible ER stress induction.

Abstract : The SAT protein of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER) and SAT deletion induces "slow spreading" phenotype. The in vitro comparison of the wild type Kresse strain and its SAT(-) knockout mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT(-) virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences were detected in the quantity and the localization of CHOP, suggesting a role of SATp in the induction of irreversible ER stress in infected cells. The involvement of irreversible ER stress induction in PT cell necrosis and the viral egress was confirmed by treatment of infected cells by ER stress inducing chemicals (MG132, DTT and Thapsigargin) that accelerated the egress and spreading both the wild type and the SAT(-) viruses. UV stress induction had no beneficial effect to PPV infectionunderscoring the specificity of ER stress pathways in the process. However, induction of CHOP and its nuclear translocation cannot alone be responsible for the biological effect of SAT, since nuclear CHOP could not complement the lack of SAT in a co-expression experiment.IMPORTANCE SATp is encoded in an alternative ORF of the PPV genome. Earlier we showed that SATp of the attenuated PPV-NADL-2 strain accumulates in the ER and accelerates virus release and spreading. Our present work revealed that "slow spreading" is a general feature of the SAT(-) PPV viruses and is the consequence of prolonged cell integrity. PPV infection induced ER stress in the infected cells regardless of SATp presence, as demonstrated by the morphological changes of the ER, and expression of the stress response proteins XBP1 and CHOP. However, the presence of SATp made the ER stress more severe and accelerated the cell death during infection as shown by the higher expression rate and the alteration of the localization of CHOP. The beneficial effect of irreversible ER stress on PPV spread was confirmed by the treatment of the infected cells with ER stress inducing chemicals.
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Submitted on : Wednesday, June 7, 2017 - 4:05:15 PM
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J. Virol.-2017-Mészáros-JV...
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István Mészáros, Renáta Tóth, Ferenc Olasz, Peter Tijssen, Zoltán Zádori. The SAT protein of porcine parvovirus accelerates viral spreading through irreversible ER stress induction.. Journal of Virology, American Society for Microbiology, 2017, ⟨10.1128/jvi.00627-17⟩. ⟨pasteur-01534474⟩



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