Abstract

Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for the avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation – either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an overview on the complement subversion mechanisms adopted by the members of various viral families including Poxviridae, Herpesviridae, Adenoviridae, Flaviviridae, Retroviridae, Picornaviridae, Astroviridae, Togaviridae, Orthomyxoviridae and Paramyxoviridae.

Highlights

  • The complement system is a constituent of the innate immunity that serves as a vital link between the innate and the adaptive immunity (Carroll and Fearon, 2004; Kolev et al, 2014)

  • It is clear from the diverse examples discussed here that to be a successful pathogen, largely viruses either acquire or encode proteins that help them subvert the complement system

  • The salient points that emerge are: (i) viruses target all the three major pathways of complement suggesting that all the pathways participate in controlling viral infections, (ii) large DNA viruses encode their own homologs of the cellular complement regulators

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Summary

INTRODUCTION

The complement system is a constituent of the innate immunity that serves as a vital link between the innate and the adaptive immunity (Carroll and Fearon, 2004; Kolev et al, 2014). This ancient system, established about 1000 million years ago (Nonaka and Kimura, 2006), has the ability to recognize and eliminate varied invading pathogens including viruses. We discuss how the complement system recognizes and neutralizes various viruses and how viruses subvert the complement assaults

RECOGNITION AND NEUTRALIZATION OF VIRUSES BY THE COMPLEMENT SYSTEM
Virus families
Togaviridae Picornaviridae Orthomyxoviridae
VIRAL STRATEGIES FOR TARGETING COMPLEMENT
Complement Subversion by Poxviruses
Complement Subversion by Herpesviruses
Complement Subversion by Adenoviruses
Complement Subversion by Flaviviruses
Complement Subversion by Hepaciviruses
Complement Subversion by Retroviruses
Complement Subversion by Picornaviruses
Complement Subversion by Astroviruses
Complement Subversion by Togaviruses
Complement Subversion by Orthomyxoviruses
Complement Subversion by Paramyxoviruses
CONCLUDING REMARKS
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