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Published in: Virology Journal 1/2023

Open Access 01-12-2023 | Vaccinia Virus | Research

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

Authors: Thiago Lima Leão, Karine Lima Lourenço, Cid de Oliveira Queiroz, Ângela Vieira Serufo, Aristóbolo Mendes da Silva, Edel F. Barbosa-Stancioli, Flávio Guimarães da Fonseca

Published in: Virology Journal | Issue 1/2023

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Abstract

Background

Cell 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).

Methods

Through 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.

Results

We 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.

Conclusions

The ATF6α sensor is robustly activated during infection while the IRE1α-XBP1 branch is down-regulated.
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Metadata
Title
Vaccinia virus induces endoplasmic reticulum stress and activates unfolded protein responses through the ATF6α transcription factor
Authors
Thiago Lima Leão
Karine Lima Lourenço
Cid de Oliveira Queiroz
Ângela Vieira Serufo
Aristóbolo Mendes da Silva
Edel F. Barbosa-Stancioli
Flávio Guimarães da Fonseca
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2023
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-023-02122-y

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