Membrane Fusion and Infection of the Influenza Hemagglutinin

  • Sean T. Smrt
  • Justin L. LorieauEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 966)


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.


Fusion peptide NMR Membrane curvature Membrane protein structure 



Bicelle Induced Curvature and Sorting


Circular Dichroism spectroscopy










Differential Scanning Calorimetry


Electron Microscopy


Electron Paramagnetic Resonance


Fusion Peptide


Fluorescence Resonance Energy Transfer


Fourier Transform Infrared spectroscopy




Hemagglutinin pre-cleavage precursor


Hemagglutinin subunit 1


Hemagglutinin subunit 2


Hemagglutinin fusion peptide domain (full-length, 23-residue form)


Hemagglutinin fusion peptide domain (truncated, 20-residue form)


Hemagglutinin transmembrane domain


type II Hexagonal inverted state


Molecular Dynamics simulations


Nuclear Magnetic Resonance spectroscopy




Negative Gaussian Curvature


Nuclear Overhauser Effect




Paramagnetic Relaxation Enhancement










Residual Dipolar Coupling




viral ribonucleoprotein complexes


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Copyright information

© Springer Internation Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Illinois at ChicagoChicagoUSA

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