Subversion of cellular stress responses by poxviruses

Abstract

Cellular stress responses are powerful mechanisms that prevent and cope with the accumulation of macromolecular damage in the cells and also boost host defenses against pathogens. Cells can initiate either protective or destructive stress responses depending, to a large extent, on the nature and duration of the stressing stimulus as well as the cell type. The productive replication of a virus within a given cell places inordinate stress on the metabolism machinery of the host and, to assure the continuity of its replication, many viruses have developed ways to modulate the cell stress responses. Poxviruses are among the viruses that have evolved a large number of strategies to manipulate host stress responses in order to control cell fate and enhance their replicative success. Remarkably, nearly every step of the stress responses that is mounted during infection can be targeted by virally encoded functions. The fine-tuned interactions between poxviruses and the host stress responses has aided virologists to understand specific aspects of viral replication; has helped cell biologists to evaluate the role of stress signaling in the uninfected cell; and has tipped immunologists on how these signals contribute to alert the cells against pathogen invasion and boost subsequent immune responses. This review discusses the diverse strategies that poxviruses use to subvert host cell stress responses.

Keywords: Poxvirus; Cell stress response; Heat shock response; Chaperones; Unfolded protein response; Host translational control; Hypoxia; Oxidative stress; DNA damage

Core tip: Poxviruses are known to encode a plethora of proteins that interact with cell biology processes in order to achieve replicative success. In this article, we review how poxviruses cope with cellular stress signals that are usually triggered upon infection to tentatively block virus replication. The understanding of mechanisms by which poxviruses and other complex viruses interfere with stress responses can further illuminate the web of pathways regulating cell homeostasis, as well as how viruses intertwine their own biochemical needs into this intricate scenario.