Abstract
Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid). We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics.
Highlights
Influenza A virus (IAV) presents an ongoing major threat to human health and there is much yet to be learned about the role of innate immunity during IAV infection [1]
There is less reason to believe that human defensins (HDs) play a role in vivo during IAV infection, they are of interest for their strong antiviral activity [8]. β-defensins are expressed predominantly by epithelial cells and are relevant in particular to IAV since they are expressed by the respiratory epithelium
Evidence suggests that surfactant protein D (SP-D) can simultaneously bind to both pathogens and neutrophil extracellular traps (NETs) [64], and we recently found that SP-D can bind to histones and inhibit histone-induced respiratory burst in neutrophils
Summary
IAV presents an ongoing major threat to human health and there is much yet to be learned about the role of innate immunity during IAV infection [1]. IAV elicits strong adaptive immune responses, it is prone to rapid genomic variation either through small incremental mutations or major changes resulting from exchange of genome segments with those of animal strains (reassortment). These genomic changes allow IAV to escape immune responses generated against prior strains. We evaluate the potential of antimicrobial peptides (AMPs) as therapies for IAV through summarizing in vitro and in vivo antiviral and immunomodulatory activity of natural and modified forms these peptides. IAV is a respiratory tract infection that rarely causes viremia or direct infection of organs outside the lung Despite this it can induce severe systemic illness largely through the production of pro-inflammatory cytokines. We will review potential means of inducing increased production of endogenous AMPs as an approach to antiviral treatment
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