Abstract
Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections remains limited and is challenged by the virus itself. While vaccination is the preferred intervention strategy against influenza, its efficacy is reduced in the elderly and infants who are most susceptible to severe and/or fatal infections. In addition, antigenic variation of IAV complicates the production of efficacious vaccines. Similarly, effectiveness of currently used antiviral drugs is jeopardized by the development of resistance to these drugs. Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections. While host-factors have long been recognized as attractive therapeutic candidates against other viruses, only recently they have been targeted for development as IAV antivirals. Future strategies to combat IAV infections will most likely include approaches that alter host-virus interactions on the one hand or dampen harmful host immune responses on the other, with the use of biological response modifiers (BRMs). In principle, BRMs are biologically active agents including antibodies, small peptides, and/or other (small) molecules that can influence the immune response. BRMs are already being used in the clinic to treat malignancies and autoimmune diseases. Repurposing such agents would allow for accelerated use against severe and potentially fatal IAV infections. In this review, we will address the potential therapeutic use of different BRM classes to modulate the immune response induced after IAV infections.
Highlights
Influenza viruses (IVs) are responsible for significant morbidity and mortality in the human population with ∼500,000 annual deaths worldwide
Recognition of IVs is mediated by pattern recognition receptors (PRRs) that include Toll like receptors (TLRs), retinoinc acid inducible gene-I (RIGI), and nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3); all of which can recognize viral RNAs during various stages of the infection cycle [3,4,5]
While the literature is largely focused on the antibacterial aspects of Antimicrobial peptides (AMPs), several studies have highlighted the antiviral potential of AMPs against several viruses including IVs [reviewed in Hsieh and Hartshorn [45]
Summary
Influenza viruses (IVs) are responsible for significant morbidity and mortality in the human population with ∼500,000 annual deaths worldwide. Recognition of IVs is mediated by pattern recognition receptors (PRRs) that include Toll like receptors (TLRs), retinoinc acid inducible gene-I (RIGI), and nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3); all of which can recognize viral RNAs during various stages of the infection cycle [3,4,5]. Activation of these sensors triggers signaling cascades that lead to the production of interferons as well as pro-inflammatory cytokines and chemokines resulting in an antiviral state within the surrounding cells/tissue [6]. BRMs are categorized based on the type of biological agent (Table 1)
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