Membrane Fusion and Infection of the Influenza Hemagglutinin

Abstract

The influenza virus is a major health concern associated with an estimated 5000 to 30,000 deaths every year (Reed et al. 2015) and a significant economic impact with the development of treatments, vaccinations and research (Molinari et al. 2007). The entirety of the influenza genome is comprised of only eleven coding genes. An enormous degree of variation in non-conserved regions leads to significant challenges in the development of inclusive inhibitors for treatment. The fusion peptide domain of the influenza A hemagglutinin (HA) is a promising candidate for treatment since it is one of the most highly conserved sequences in the influenza genome (Heiny et al. 2007), and it is vital to the viral life cycle. Hemagglutinin is a class I viral fusion protein that catalyzes the membrane fusion process during cellular entry and infection. Impediment of the hemagglutinin's function, either through incomplete post-translational processing (Klenk et al. 1975; Lazarowitz and Choppin 1975) or through mutations (Cross et al. 2001), leads to non-infective virus particles. This review will investigate current research on the role of hemagglutinin in the virus life cycle, its structural biology and mechanism as well as the central role of the hemagglutinin fusion peptide (HAfp) to influenza membrane fusion and infection.

Role of Protein Glycosylation in Host-Pathogen Interaction

“…One typical example is the Influenza Virus (IAVs) surface glycoprotein haemagglutinin (HA). It is a trimeric lectin in IAVs that can help host recognition and further cytoplasm penetration through binding SA-containing glycoproteins on host cell membranes [195,196]. The subtypes of IAVs vary in host ranges depend on specific host recognition of HA [197], especially the differences in the glycosidic bonds of penultimate carbohydrate of the SA residue [198,199].…”

Lipid-dependence of target membrane stability during influenza viral fusion

“…For influenza virus, fusion between viral and endosomal membranes is mediated by the surface glycoprotein hemagglutinin (HA) triggered by a decrease in endosomal pH that induces a conformational change in HA. Although influenza is a global health concern, one of the most widely studied viruses and considered a paradigm for biological fusion, molecular details about the influenza HA-mediated fusion remain elusive (Hamilton et al, 2012;Smrt and Lorieau, 2017).…”

Study on the Antiviral Activities and Hemagglutinin-Based Molecular Mechanism of Novel Chlorogenin 3-O-β-Chacotrioside Derivatives against H5N1 Subtype Viruses

“…The fusion peptide domain of HA has the most highly conserved sequences, and it is vital to the viral life cycle, pathogenicity, and virulence. It has been documented that the fusion peptide domain of influenza HA is a promising candidate target for the prevention/control of viral infection [19,38].…”

“…Hemagglutinin (HA) is a crucial viral envelope spike glycoprotein, responsible for entry and infection of viruses into host cells via binding to sialic acid on the surface of target cells. The fusion peptide domain genome of HA has the most highly conserved sequences and is vital to the viral life cycle [18][19][20]. Thus, targeting at HA may be a highly effective influenza therapeutic strategy.…”