Poxviruses and Immune Evasion

Abstract

Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host

“…These include expressing inhibitors of the antiviral pathways of the cell, preventing the cell death of the infected cell and the encoding anti-inflammatory proteins to dampen the host defenses mounted against it. These immunomodulatory proteins often mediate pathogenesis induced by these viruses [87] and some will be discussed in greater detail in the next sections.…”

“…Successful viral replication can be attributed to the ability of the MV to avoid recognition and clearance by the host innate and acquired immune systems of the infected rabbit [47,87]. A wide variety of MV encoded immunoregulatory proteins have been identified which include; virokines, viroreceptors, proteins that modulate host range and/or apoptotic response and proteins that modulate the action of macrophages and T cells (Tab.…”

“…There are many extensive and excellent reviews on the immunomodulatory proteins of poxviruses [42,50,64,69,74,75,87,91,106]. This review will focus primarily on the interactions of MV and its susceptible host, the European rabbit in vitro and in vivo.…”

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

“…Although considered highly safe in humans, vaccination with VV strains can cause significant and fatal complications especially in immunocompromised hosts and young children [22]. VV possesses an enormously variable set of immune evasion mechanisms, including interactions with complement, cytokines and chemokines [23][24][25][26][27], potentially causing immunosuppression of the host. At a cellular level in particular, DC, the sentinels of the immune system, are targeted by numerous viral strategies aiming to inhibit an anti-viral immune response [28].…”

Innate immune activation of NFκB and its antagonism by poxviruses

“…Apart from inhibiting intracellular signalling to NFkB by IL-1 and TNFa, poxviruses also target these cytokines by expressing poxvirally-encoded secreted binding proteins and receptors from infected cells, which inhibit the cell surface binding of the IL-1 family (IL-1b and IL-18) and of the TNF family (TNFa, Lymphotoxin-a, CD153) [97]. Some poxvirally-encoded TNF-binding proteins resemble a soluble TNFR (vTNFRs) with varying degrees of ligand specificity and affinity [98] while some do not directly resemble the TNFR and are therefore referred to as 'TNF binding proteins' (vTNF-BPs) [99].…”