Influenza virus binds its host cell using multiple dynamic interactions

Sieben, Christian; Kappel, Christian; Zhu, Rong; Woźniak, Anna; Rankl, Christian; Hinterdorfer, Peter; Grubmüller, Helmut; Herrmann, Andreas

doi:10.1073/pnas.1120265109

Cited by 130 publications

(118 citation statements)

References 35 publications

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“…The dissociation coefficient (Kd) between HA and its receptor is 1.4–6.5 × 10 −3 M1112, which is 1 × 10 5 –10 11 -fold greater than the Kd of adhesive proteins on other viruses (e.g., the E2 protein of SFV and the G protein of VSV) or the Kd of several physiological ligands (Supplementary Table S1)131415161718. Moreover, the HA-receptor binding half-life is 0.8–5.5 s19, whereas the half-life of influenza virus internalisation is 10–15 min20. Therefore, stable association of IAV with the cell surface requires multiple HA-receptor binding events.…”

mentioning

confidence: 94%

Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery

Sakai

Nishimura²,

Naito

et al. 2017

Sci Rep

127

144

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Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.

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mentioning

confidence: 94%

Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery

Sakai

Nishimura²,

Naito

et al. 2017

Sci Rep

127

144

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“…Recently Sieben et al . [30] determined the force of the interaction between HA and sialic acid on the cell membrane using optical tweezers and an HA-coated bead. By contrast, we developed a novel method, using optical tweezers to trap heterogeneous virus particles.…”

Section: Discussionmentioning

confidence: 99%

A Novel Single Virus Infection System Reveals That Influenza Virus Preferentially Infects Cells in G1 Phase

et al. 2013

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BackgroundInfluenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA), a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized.Methods/ResultsTo resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm) at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1) the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins) than the membranes of cells in S/G2/M-phase; 2) the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3) S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition.ConclusionsA novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

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“…All-atom MD simulations have been applied to numerous crystal complexes of HAs with receptor analogues to characterize binding mode dynamics, as well as to study recognition and specificity based on bound receptor conformations and interaction profiles [8, 9, 10, 11, 12]. Recent modeling and simulation work has also revealed that HA receptor specificity may depend on extended glycan structure and the ability to accommodate bidentate binding to biantennary glycans [13, 14].…”

Section: Envelope Proteinsmentioning

confidence: 99%

All-atom virus simulations

Hadden

Perilla

2018

Current Opinion in Virology

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The constant threat of viral disease can be combated by the development of novel vaccines and therapeutics designed to disrupt key features of virus structure or infection cycle processes. Such development relies on high-resolution characterization of viruses and their dynamical behaviors, which are often challenging to obtain solely by experiment. In response, all-atom molecular dynamics simulations are widely leveraged to study the structural components of viruses, leading to some of the largest simulation endeavors undertaken to date. The present work reviews exemplary all-atom simulation work on viruses, as well as progress toward simulating entire virions.

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Influenza virus binds its host cell using multiple dynamic interactions

Cited by 130 publications

References 35 publications

Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery

Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery

A Novel Single Virus Infection System Reveals That Influenza Virus Preferentially Infects Cells in G1 Phase

All-atom virus simulations

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