Conserved stem fragment from H3 influenza hemagglutinin elicits cross-clade neutralizing antibodies through stalk-targeted blocking of conformational change during membrane fusion

2016 ◽  
Vol 172 ◽  
pp. 11-20 ◽  
Author(s):  
Xin Gong ◽  
He Yin ◽  
Yuhua Shi ◽  
Shanshan Guan ◽  
Xiaoqiu He ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Conformational Change ◽  
Neutralizing Antibodies ◽  
Influenza Hemagglutinin ◽  
Stem Fragment

scholarly journals Discovering neutralizing antibodies targeting the stem epitope of H1N1 influenza hemagglutinin with synthetic phage-displayed antibody libraries

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Chao-Ping Tung ◽  
Ing-Chien Chen ◽  
Chung-Ming Yu ◽  
Hung-Pin Peng ◽  
Jhih-Wei Jian ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
H1n1 Influenza ◽  
Influenza Hemagglutinin ◽  
Antibody Libraries

Insights into a Structure-Based Mechanism of Viral Membrane Fusion

2000 ◽  
Vol 20 (6) ◽  
pp. 557-570 ◽  
Author(s):  
Danika L. LeDuc ◽  
Yeon-Kyun Shin
Keyword(s):  
Membrane Fusion ◽  
General Structure ◽  
Viral Membrane ◽  
Induced Membrane ◽  
Alternative Scenario ◽  
Influenza Hemagglutinin ◽  
Hiv Gp120 ◽  
Viral Membrane Fusion ◽  
Spike Proteins

A number of different viral spike proteins, responsible for membrane fusion, show striking similarities in their core structures. The prospect of developing a general structure-based mechanism seems plausible in light of these newly determined structures. Influenza hemagglutinin (HA) is the best-studied fusion machine, whose action has previously been described by a hypothetical “spring-loaded” model. This model has recently been extended to explain the mechanism of other systems, such as HIV gp120–gp41. However, evidence supporting this idea is insufficient, requiring re-examination of the mechanism of HA-induced membrane fusion. Recent experiments with a shortened construct of HA, which is able to induce lipid mixing, have provided evidence for an alternative scenario for HA-induced membrane fusion and perhaps that of other viral systems.

Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions

2021 ◽  
Author(s):  
Ali Zhang ◽  
Hanu Chaudhari ◽  
Yonathan Agung ◽  
Michael D'Agostino ◽  
Jann Ang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
Influenza Virus Infection ◽  
Dependent Manner ◽  
Neuraminidase Inhibitors ◽  
Immune Effector ◽  
Effector Cells ◽  
Individual Level ◽  
Influenza Hemagglutinin ◽  
Stalk Domain

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

scholarly journals Hemagglutinin-Mediated Membrane Fusion: A Biophysical Perspective

2018 ◽  
Vol 47 (1) ◽  
pp. 153-173 ◽  
Author(s):  
Sander Boonstra ◽  
Jelle S. Blijleven ◽  
Wouter H. Roos ◽  
Patrick R. Onck ◽  
Erik van der Giessen ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Host Cell ◽  
Conformational Changes ◽  
Fusion Process ◽  
Host Cell Membrane ◽  
Activation Barriers ◽  
Viral Membrane ◽  
Influenza Hemagglutinin ◽  
Working Together

Influenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion. Furthermore, we highlight the role of novel single-particle experiments and computational approaches in understanding the fusion process and their complementarity with other biophysical approaches.

scholarly journals An Investigation of the Influenza Hemagglutinin Membrane Fusion Process using Microsecond-Level MD Simulations

2020 ◽  
Vol 118 (3) ◽  
pp. 57a
Author(s):  
Vivek Govind Kumar ◽  
Dylan S. Ogden ◽  
Adithya Polasa ◽  
Mahmoud Moradi
Keyword(s):  
Membrane Fusion ◽  
Md Simulations ◽  
Fusion Process ◽  
Influenza Hemagglutinin

scholarly journals Membrane Fusion by Single Influenza Hemagglutinin Trimers

2006 ◽  
Vol 281 (18) ◽  
pp. 12729-12735 ◽  
Author(s):  
Masaki Imai ◽  
Takafumi Mizuno ◽  
Kazunori Kawasaki
Keyword(s):  
Membrane Fusion ◽  
Influenza Hemagglutinin

Cholesterol Promotes Hemifusion and Pore Widening in Membrane Fusion Induced by Influenza Hemagglutinin

2008 ◽  
Vol 205 (5) ◽  
pp. i12-i12
Author(s):  
Subrata Biswas ◽  
Shu-Rong Yin ◽  
Paul S. Blank ◽  
Joshua Zimmerberg
Keyword(s):  
Membrane Fusion ◽  
Influenza Hemagglutinin ◽  
Pore Widening
Sign in / Sign up

Export Citation Format

Share Document