Structural Insights into the Membrane Fusion Mechanism Mediated by Influenza Virus Hemagglutinin

ABSTRACT Influenza virus hemagglutinin (HA) is a determinant of virus infectivity. Therefore, it is important to determine whether HA of a new influenza virus, which can potentially cause pandemics, is functional against human cells. The novel imaging technique reported here allows rapid analysis of HA function by visualizing viral fusion inside cells. This imaging was designed to detect fusion changing the spectrum of the fluorescence-labeled virus. Using this imaging, we detected the fusion between a virus and a very small endosome that could not be detected previously, indicating that the imaging allows highly sensitive detection of viral fusion.

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Deacylation of influenza virus hemagglutinin does not affect the kinetics of low pH induced membrane fusion

Pflügers Archiv - European Journal of Physiology ◽

10.1007/bf02346366 ◽

1996 ◽

Vol 431 (S6) ◽

pp. R257-R258 ◽

Cited By ~ 1

Author(s):

Britta Schroth ◽

Hans C. Philipp ◽

Michael Veit ◽

Michael F. G. Schmidt ◽

Andreas Herrmann

Keyword(s):

Influenza Virus ◽

Membrane Fusion ◽

Low Ph ◽

Induced Membrane ◽

Influenza Virus Hemagglutinin ◽

Kinetics Of

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Membrane Structures of the Hemifusion-Inducing Fusion Peptide Mutant G1S and theFusion-Blocking Mutant G1V of Influenza Virus HemagglutininSuggest a Mechanism for Pore Opening in MembraneFusion

Journal of Virology ◽

10.1128/jvi.79.18.12065-12076.2005 ◽

2005 ◽

Vol 79 (18) ◽

pp. 12065-12076 ◽

Cited By ~ 51

Author(s):

Yinling Li ◽

Xing Han ◽

Alex L. Lai ◽

John H. Bushweller ◽

David S. Cafiso ◽

...

Keyword(s):

Influenza Virus ◽

Membrane Fusion ◽

Lipid Bilayer ◽

Membrane Surface ◽

Helical Structure ◽

Fusion Peptide ◽

Membrane Structures ◽

Influenza Virus Hemagglutinin ◽

Target Membrane ◽

Pore Opening

ABSTRACT Influenza virus hemagglutinin (HA)-mediated membrane fusion is initiated by a conformational change that releases a V-shaped hydrophobic fusion domain, the fusion peptide, into the lipid bilayer of the target membrane. The most N-terminal residue of this domain, a glycine, is highly conserved and is particularly critical for HA function; G1S and G1V mutant HAs cause hemifusion and abolish fusion, respectively. We have determined the atomic resolution structures of the G1S and G1V mutant fusion domains in membrane environments. G1S forms a V with a disrupted “glycine edge” on its N-terminal arm and G1V adopts a slightly tilted linear helical structure in membranes. Abolishment of the kink in G1V results in reduced hydrophobic penetration of the lipid bilayer and an increased propensity to formβ -structures at the membrane surface. These results underline the functional importance of the kink in the fusion peptide and suggest a structural role for the N-terminal glycine ridge in viral membrane fusion.

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Fatty acids on the A/Japan/305/57 influenza virus hemagglutinin have a role in membrane fusion.

The EMBO Journal ◽

10.1002/j.1460-2075.1990.tb07604.x ◽

1990 ◽

Vol 9 (12) ◽

pp. 3857-3866 ◽

Cited By ~ 69

Author(s):

C. W. Naeve ◽

D. Williams

Keyword(s):

Fatty Acids ◽

Influenza Virus ◽

Membrane Fusion ◽

Influenza Virus Hemagglutinin

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Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Molecular Biology of the Cell ◽

10.1091/mbc.10.6.1821 ◽

1999 ◽

Vol 10 (6) ◽

pp. 1821-1836 ◽

Cited By ~ 95

Author(s):

Grigory B. Melikyan ◽

Sasa Lin ◽

Michael G. Roth ◽

Fredric S. Cohen

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Amino Acid Sequence ◽

Membrane Fusion ◽

Integral Membrane Protein ◽

Wild Type ◽

Influenza Virus Hemagglutinin ◽

Tm Domain ◽

Fusion Pores ◽

Sequence Requirements

The amino acid sequence requirements of the transmembrane (TM) domain and cytoplasmic tail (CT) of the hemagglutinin (HA) of influenza virus in membrane fusion have been investigated. Fusion properties of wild-type HA were compared with those of chimeras consisting of the ectodomain of HA and the TM domain and/or CT of polyimmunoglobulin receptor, a nonviral integral membrane protein. The presence of a CT was not required for fusion. But when a TM domain and CT were present, fusion activity was greater when they were derived from the same protein than derived from different proteins. In fact, the chimera with a TM domain of HA and truncated CT of polyimmunoglobulin receptor did not support full fusion, indicating that the two regions are not functionally independent. Despite the fact that there is wide latitude in the sequence of the TM domain that supports fusion, a point mutation of a semiconserved residue within the TM domain of HA inhibited fusion. The ability of a foreign TM domain to support fusion contradicts the hypothesis that a pore is composed solely of fusion proteins and supports the theory that the TM domain creates fusion pores after a stage of hemifusion has been achieved.

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