Viral Evasion of the Complement System and Its Importance for Vaccines and Therapeutics.

Jack Mellors,Miles Carroll,Tom Tipton,Stephanie Longet

doi:10.3389/fimmu.2020.01450

Jack Mellors, Miles Carroll + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2020.01450

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Abstract

The complement system is a key component of innate immunity which readily responds to invading microorganisms. Activation of the complement system typically occurs via three main pathways and can induce various antimicrobial effects, including: neutralization of pathogens, regulation of inflammatory responses, promotion of chemotaxis, and enhancement of the adaptive immune response. These can be vital host responses to protect against acute, chronic, and recurrent viral infections. Consequently, many viruses (including dengue virus, West Nile virus and Nipah virus) have evolved mechanisms for evasion or dysregulation of the complement system to enhance viral infectivity and even exacerbate disease symptoms. The complement system has multifaceted roles in both innate and adaptive immunity, with both intracellular and extracellular functions, that can be relevant to all stages of viral infection. A better understanding of this virus-host interplay and its contribution to pathogenesis has previously led to: the identification of genetic factors which influence viral infection and disease outcome, the development of novel antivirals, and the production of safer, more effective vaccines. This review will discuss the antiviral effects of the complement system against numerous viruses, the mechanisms employed by these viruses to then evade or manipulate this system, and how these interactions have informed vaccine/therapeutic development. Where relevant, conflicting findings and current research gaps are highlighted to aid future developments in virology and immunology, with potential applications to the current COVID-19 pandemic.

Highlights

The complement system is a heat-labile component of native plasma involving both extracellular and cell surface membrane-associated proteins which form a major constituent of the innate immune response
Activation of the complement system typically occurs via three distinct target recognition pathways which converge at a single point; the cleavage of complement component 3 (C3)
Some aspects of the complement system can suppress certain responses of adaptive immunity: stimulation of Complement receptor 3 (CR3) on dendritic cells (DCs) can suppress the release of inflammatory cytokines [98] and C1q-differentiated DCs demonstrate an increased phagocytic capacity but reduced expression of CD80, CD83, and CD86 required for T cell activation [223]

Summary

Introduction

The complement system is a heat-labile component of native plasma involving both extracellular and cell surface membrane-associated proteins which form a major constituent of the innate immune response. Infected host cells which present viral antigens on the cell surface membrane can activate the classical pathway, as the antigens bind IgM/IgG to induce complement dependent cytotoxicity (CDC). Broadly neutralizing anti-HIV-1 antibodies can bind the viral envelope protein expressed on infected primary lymphocytes to initiate complement deposition.

Results

Conclusion