Vaccinia virus induces endoplasmic reticulum stress and activates unfolded protein responses through the ATF6α transcription factor

Virology Journal

Research

Cid de Oliveira Queiroz¹  Ângela Vieira Serufo¹  Thiago Lima Leão¹  Karine Lima Lourenço¹  Flávio Guimarães da Fonseca¹  Edel F. Barbosa-Stancioli¹  Aristóbolo Mendes da Silva² 

[1] Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;

关键词: Vaccinia virus;    Cell stress;    Endoplasmic reticulum stress;    Unfolded protein response;    MVA;    WR;   

DOI  :  10.1186/s12985-023-02122-y

 received in 2023-05-09, accepted in 2023-07-08,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCell responses to different stress inducers are efficient mechanisms that prevent and fight the accumulation of harmful macromolecules in the cells and also reinforce the defenses of the host against pathogens. Vaccinia virus (VACV) is an enveloped, DNA virus, belonging to the Poxviridae family. Members of this family have evolved numerous strategies to manipulate host responses to stress controlling cell survival and enhancing their replicative success. In this study, we investigated the activation of the response signaling to malformed proteins (UPR) by the VACV virulent strain—Western Reserve (WR)—or the non-virulent strain—Modified Vaccinia Ankara (MVA).MethodsThrough RT-PCR RFLP and qPCR assays, we detected negative regulation of XBP1 mRNA processing in VACV-infected cells. On the other hand, through assays of reporter genes for the ATF6 component, we observed its translocation to the nucleus of infected cells and a robust increase in its transcriptional activity, which seems to be important for virus replication. WR strain single-cycle viral multiplication curves in ATF6α-knockout MEFs showed reduced viral yield.ResultsWe observed that VACV WR and MVA strains modulate the UPR pathway, triggering the expression of endoplasmic reticulum chaperones through ATF6α signaling while preventing IRE1α-XBP1 activation.ConclusionsThe ATF6α sensor is robustly activated during infection while the IRE1α-XBP1 branch is down-regulated.

【 授权许可】

CC BY   
© The Author(s) 2023

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