ABSTRACT
Influenza A virus (IAV) is a member of the single-stranded RNA (ssRNA) family of viruses. The most recent global pandemic caused by the SARS-CoV-2 virus has shown the major threat that RNA viruses can pose to humanity. In comparison, influenza has an even higher pandemic potential as a result of its high rate of mutations within its relatively short (<13 kbp) genome, as well as its capability to undergo genetic reassortment. In light of this threat, and the fact that RNA structure is connected to a broad range of known biological functions, deeper investigation of viral RNA (vRNA) structures is of high interest. Here, for the first time, we propose a secondary structure for segment 8 vRNA (vRNA8) of A/California/04/2009 (H1N1) formed in the presence of cellular and viral components. This structure shows similarities with prior in vitro experiments. Additionally, we determined the location of several well-defined, conserved structural motifs of vRNA8 within IAV strains with possible functionality. These RNA motifs appear to fold independently of regional nucleoprotein (NP)-binding affinity, but a low or uneven distribution of NP in each motif region is noted. This research also highlights several accessible sites for oligonucleotide tools and small molecules in vRNA8 in a cellular environment that might be a target for influenza A virus inhibition on the RNA level.
Subject(s)
Gene Expression Regulation, Viral , Genome, Viral/genetics , Influenza A Virus, H1N1 Subtype/genetics , Nucleic Acid Conformation , RNA, Viral/chemistry , Animals , Base Sequence , Dogs , Humans , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/virology , Madin Darby Canine Kidney Cells , Models, Molecular , Nucleotide Motifs/genetics , RNA Folding , RNA, Viral/genetics , Viral Proteins/genetics , Viral Proteins/metabolismABSTRACT
Influenza virus has the potential for being one of the deadliest viruses, as we know from the pandemic's history. The influenza virus, with a constantly mutating genome, is becoming resistant to existing antiviral drugs and vaccines. For that reason, there is an urgent need for developing new therapeutics and therapies. Despite the fact that a new generation of universal vaccines or anti-influenza drugs are being developed, the perfect remedy has still not been found. In this review, various strategies for using nanoparticles (NPs) to defeat influenza virus infections are presented. Several categories of NP applications are highlighted: NPs as immuno-inducing vaccines, NPs used in gene silencing approaches, bare NPs influencing influenza virus life cycle and the use of NPs for drug delivery. This rapidly growing field of anti-influenza methods based on nanotechnology is very promising. Although profound research must be conducted to fully understand and control the potential side effects of the new generation of antivirals, the presented and discussed studies show that nanotechnology methods can effectively induce the immune responses or inhibit influenza virus activity both in vitro and in vivo. Moreover, with its variety of modification possibilities, nanotechnology has great potential for applications and may be helpful not only in anti-influenza but also in the general antiviral approaches.