Next Article in Journal
Complete Nucleotide Sequence of Watermelon Chlorotic Stunt Virus Originating from Oman
Previous Article in Journal
T Cell Memory in the Context of Persistent Herpes Viral Infections
Previous Article in Special Issue
Herpes Virus Fusion and Entry: A Story with Many Characters
Viruses 2012, 4(7), 1144-1168; doi:10.3390/v4071144
Review

Influenza Virus-Mediated Membrane Fusion: Determinants of Hemagglutinin Fusogenic Activity and Experimental Approaches for Assessing Virus Fusion

1
, 1,*  and 2
Received: 7 June 2012; in revised form: 11 July 2012 / Accepted: 17 July 2012 / Published: 24 July 2012
(This article belongs to the Special Issue Virus-Induced Membrane Fusion)
View Full-Text   |   Download PDF [889 KB, uploaded 24 July 2012]   |   Browse Figures
Abstract: Hemagglutinin (HA) is the viral protein that facilitates the entry of influenza viruses into host cells. This protein controls two critical aspects of entry: virus binding and membrane fusion. In order for HA to carry out these functions, it must first undergo a priming step, proteolytic cleavage, which renders it fusion competent. Membrane fusion commences from inside the endosome after a drop in lumenal pH and an ensuing conformational change in HA that leads to the hemifusion of the outer membrane leaflets of the virus and endosome, the formation of a stalk between them, followed by pore formation. Thus, the fusion machinery is an excellent target for antiviral compounds, especially those that target the conserved stem region of the protein. However, traditional ensemble fusion assays provide a somewhat limited ability to directly quantify fusion partly due to the inherent averaging of individual fusion events resulting from experimental constraints. Inspired by the gains achieved by single molecule experiments and analysis of stochastic events, recently-developed individual virion imaging techniques and analysis of single fusion events has provided critical information about individual virion behavior, discriminated intermediate fusion steps within a single virion, and allowed the study of the overall population dynamics without the loss of discrete, individual information. In this article, we first start by reviewing the determinants of HA fusogenic activity and the viral entry process, highlight some open questions, and then describe the experimental approaches for assaying fusion that will be useful in developing the most effective therapies in the future.
Keywords: influenza virus; hemagglutinin; membrane fusion; protease; virus entry influenza virus; hemagglutinin; membrane fusion; protease; virus entry
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Hamilton, B.S.; Whittaker, G.R.; Daniel, S. Influenza Virus-Mediated Membrane Fusion: Determinants of Hemagglutinin Fusogenic Activity and Experimental Approaches for Assessing Virus Fusion. Viruses 2012, 4, 1144-1168.

AMA Style

Hamilton BS, Whittaker GR, Daniel S. Influenza Virus-Mediated Membrane Fusion: Determinants of Hemagglutinin Fusogenic Activity and Experimental Approaches for Assessing Virus Fusion. Viruses. 2012; 4(7):1144-1168.

Chicago/Turabian Style

Hamilton, Brian S.; Whittaker, Gary R.; Daniel, Susan. 2012. "Influenza Virus-Mediated Membrane Fusion: Determinants of Hemagglutinin Fusogenic Activity and Experimental Approaches for Assessing Virus Fusion." Viruses 4, no. 7: 1144-1168.


Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert