title: 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.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA.
authors.forename: Sean T
authors.initials: ST
authors.lastname: Smrt
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA. justin@lorieau.com.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Lorieau
mesh_terms: D000818:Animals; D015195:Drug Design; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D008958:Models, Molecular; D000072417:Protein Domains; D013329:Structure-Activity Relationship; D065147:Viral Fusion Protein Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D014774:Virulence; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D065147:Viral Fusion Protein Inhibitors; D014760:Viral Fusion Proteins
keywords: Fusion peptide; Membrane curvature; Membrane protein structure; NMR