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Vaccinia virus activation and antagonism of cytosolic DNA sensing

El-Jesr, Misbah, Teir, Muad and Maluquer de Motes, Carlos (2020) Vaccinia virus activation and antagonism of cytosolic DNA sensing Frontiers in Immunology.

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Abstract

Cells express multiple molecules aimed at detecting incoming virus and infection. Recognition of virus infection leads to the production of cytokines, chemokines and restriction factors that limit virus replication and activate an adaptive immune response offering long-term protection. Recognition of cytosolic DNA has become a central immune sensing mechanism involved in infection, autoinflammation and cancer immunotherapy. Vaccinia virus (VACV) is the prototypic member of the family Poxviridae and the vaccine used to eradicate smallpox. VACV harbours enormous potential as a vaccine vector and several attenuated strains are currently being developed against infectious diseases. In addition, VACV has emerged as a popular oncolytic agent due to its cytotoxic capacity even in hypoxic environments. As a poxvirus, VACV is an unusual virus that replicates its large DNA genome exclusively in the cytoplasm of infected cells. Despite producing large amounts of cytosolic DNA, VACV efficiently suppresses the subsequent innate immune response by deploying an arsenal of proteins with capacity to disable host antiviral signalling, some of which specifically target cytosolic DNA sensing pathways. Some of these strategies are conserved amongst orthopoxviruses, whereas others are seemingly unique to VACV. In this review we provide an overview of the VACV replicative cycle and discuss the recent advances on our understanding of how VACV induces and antagonises innate immune activation via cytosolic DNA sensing pathways. The implications of these findings in the rational design of vaccines and oncolytics based on VACV are also discussed.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
El-Jesr, Misbah
Teir, Muad
Maluquer de Motes, Carlosc.maluquerdemotes@surrey.ac.uk
Date : 1 October 2020
Funders : Biotechnology and Biological Sciences Research Council (BBSRC)
DOI : 10.3389/fimmu.2020.568412
Copyright Disclaimer : © 2020 El-Jesr, Teir and Maluquer de Motes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Related URLs :
Depositing User : Clive Harris
Date Deposited : 02 Oct 2020 11:35
Last Modified : 02 Oct 2020 11:42
URI: http://epubs.surrey.ac.uk/id/eprint/858633

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