New Insights into the Spring-Loaded Conformational Change of Influenza Virus Hemagglutinin

Gruenke, Jennifer A.; Armstrong, R. Todd; Newcomb, William W.; Brown, Jay C.; White, Judith M.

doi:10.1128/jvi.76.9.4456-4466.2002

Cited by 62 publications

(66 citation statements)

References 33 publications

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“…Peptides to this region will be useful probes to explore molecular mechanisms of how HSV induces membrane fusion. As with HIV and other viruses, the site at which an inhibitory peptide engages the virus could be a vulnerable target site to develop potent antiviral agents (5,13,17).…”

Section: Discussionmentioning

confidence: 99%

“…Some synthetic peptides to coiled coils in viral proteins block membrane fusion mediated by these glycoproteins. For influenza virus HA or HIV gp41, peptides to defined ␣-helix regions interfere with fusion between the virus envelope and a cell membrane (5,13). A synthetic peptide that mimics the predicted coiled coil of B5 specifically inhibits HSV stable binding and entry into B5 polyclonal or transiently transfected porcine cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A New Class of Receptor for Herpes Simplex Virus Has Heptad Repeat Motifs That Are Common to Membrane Fusion Proteins

Perez¹,

Li²,

Pérez‐Romero³

et al. 2005

J Virol

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We isolated a human cDNA by expression cloning and characterized its gene product as a new human protein that enables entry and infection of herpes simplex virus (HSV). The gene, designated hfl-B5, encodes a type II cell surface membrane protein, B5, that is broadly expressed in human primary tissue and cell lines. It contains a high-scoring heptad repeat at the extracellular C terminus that is predicted to form an ␣-helix for coiled coils like those in cellular SNAREs or in some viral fusion proteins. A synthetic 30-mer peptide that has the same sequence as the heptad repeat ␣-helix blocks HSV infection of B5-expressing porcine cells and human HEp-2 cells. Transient expression of human B5 in HEp-2 cells results in increased polykarocyte formation even in the absence of viral proteins. The B5 protein fulfills all criteria as a receptor or coreceptor for HSV entry. Use by HSV of a human cellular receptor, such as B5, that contains putative membrane fusion domains provides an example where a pathogenic virus with broad tropism has usurped a widely expressed cellular protein to function in infection at events that lead to membrane fusion.Herpes simplex virus type 1 (HSV-1) and HSV-2 are prevalent human pathogens that infect a broad range of animal cells. They establish lifelong latency in human neurons from which reactivation to lytic replication leads to recurrent herpes lesions. Entry into cells involves attachments of viral glycoproteins to multiple alternative cellular receptors (2,10,30). However, the molecular mechanisms of entry have not yet been defined.The human proteins identified as receptors for HSV include heparan sulfate (HS) proteoglycans and several integral membrane proteins that are members of well-characterized families (30). Herpesvirus entry mediator HVEM (HveA) is a member of the tumor necrosis factor receptor family (20). Nectin 2 (HveB) and nectin 1 (HveC) or herpes immunoglobulin-like receptor are adhesion molecules in the immunoglobulin superfamily (7,12,35). D-Glucosaminyl 3-O-sulfotransferase (3-OS) modifies specific sites in cellular HS to generate binding sites for the essential HSV attachment glycoprotein D (gD) (27). Nectin 1, which was originally isolated as poliovirus receptorrelated protein, allows entry of most HSV-1 and HSV-2 strains and is broadly expressed on a range of human tissues. HVEM and nectin 2 are more limited by either tissue distribution or strain specificity for transfer of HSV susceptibility. HVEM does not support entry of mutant virus HSV-1(Rid-1) that has a point mutation in gD (20). Nectin 2 is reported to allow entry of HSV-2 strains and HSV-1(Rid-1), but not most HSV-1 strains (35). Isolation of animal homologs for nectin 1 and HVEM raises the possibility that they may engage HSV during infection of animal cells.With the exception of HS, HSV gD is a viral ligand for these receptors. Some regions of gD involved in receptor interactions have been defined (3,8). How the cellular proteins interact with other viral proteins (each other or other cellular proteins) ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A New Class of Receptor for Herpes Simplex Virus Has Heptad Repeat Motifs That Are Common to Membrane Fusion Proteins

Perez¹,

Li²,

Pérez‐Romero³

et al. 2005

J Virol

View full text Add to dashboard Cite

show abstract

“…Mechanistically, this can be done by ligand recognition, protein conformational changes, or posttranslational modifications (PTMs). [1][2][3][4][5] PTMs are especially important in the molecular communication across cellular processes, including signal transduction and the host response to viral infection. [6][7][8][9][10][11][12][13] Viruses must utilize this form of cellular communication for their own nefarious purposes.…”

Section: Introductionmentioning

confidence: 99%

<div>Phosphorylation of the viral coat protein regulates RNA virus infection</div>

Hoover

Kao

2016

VAAT

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“…White and coworkers have suggested that HA undergoes a spring-loaded conformational change and HA aggregates to form rosette formation (Gruenke et al 2002). The full-length of the cytoplasmic tail of HA has been estimated to be less than 1 nm (Naeve and Williams 1990), whereas the dimensions of GFP are approximately 2.5ϫ2.5ϫ4.5 nm 3 (Yang et al 1996).…”

mentioning

confidence: 99%

Enlargement of Influenza Virus Hemagglutinin Cytoplasmic Tail by Tagging with an Enhanced Green Fluorescent Protein Interferes with Hemagglutinin-mediated Membrane Fusion Prior to the Lipid-mixing Step

et al. 2010

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SummaryThe cytoplasmic tail (CT) of the influenza virus hemagglutinin (HA) consists of an amino acid sequence that is highly conserved among various subtypes of the influenza A virus. To study the effect of CT size on HA-mediated membrane fusion, we constructed a cDNA encoding a chimeric protein in which the size of CT of influenza virus HA (from A/Hong Kong/1/68; subtype H3) was enlarged by tagging with enhanced green fluorescent protein (EGFP). The EGFP-tagged HA (HA-EGFP) or wild-type HA was individually expressed in HeLa cells, and cell membrane fusion activities were examined using dual-labeled chicken red blood cells. The red blood cells were labeled with both lipidic and aqueous dyes to verify the fusion activity of the HA-EGFP at different steps of the fusion process: 1) lipid-mixing, 2) content-mixing and 3) fusion pore formation. Our data showed that the binding activity of HA towards red blood cells was not affected by enlargement of the CT of HA with EGFP. However, its lipid-mixing, subsequent content-mixing, and fusion pore formation activities were drastically impaired by the enlargement. Therefore, we conclude that CT size is crucial for progression from the binding step to the lipid-mixing step in the process of HAmediated membrane fusion.

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New Insights into the Spring-Loaded Conformational Change of Influenza Virus Hemagglutinin

Cited by 62 publications

References 33 publications

A New Class of Receptor for Herpes Simplex Virus Has Heptad Repeat Motifs That Are Common to Membrane Fusion Proteins

A New Class of Receptor for Herpes Simplex Virus Has Heptad Repeat Motifs That Are Common to Membrane Fusion Proteins

<div>Phosphorylation of the viral coat protein regulates RNA virus infection</div>

Enlargement of Influenza Virus Hemagglutinin Cytoplasmic Tail by Tagging with an Enhanced Green Fluorescent Protein Interferes with Hemagglutinin-mediated Membrane Fusion Prior to the Lipid-mixing Step

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