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A viral grappling hook: Flu virus attacks like a pirate boarding party

A viral grappling hook: Flu virus attacks like a pirate boarding party | Influenza | Scoop.it

Viruses are biological pirates, invading cells and hijacking their machinery to reproduce and infect again. Research at Harvard Medical School is shedding new light on the battle line where viral and cell membranes meet, and the key role of a protein grappling hook with which the influenza virus commandeers its prize—your cells.

An influenza virus is a collection of eight RNA strands enclosed in a lipid-bilayer membrane. When the virus encounters a cell—in your lung, for example—that cell may engulf the virus inside an internal membrane called an endosome. To escape that bubble, the virus fuses its membrane with the endosome's, opening a window into the cell's interior. Once free, the viral RNA is copied, and the hijacked cell begins to manufacture copies of the virus. To fuse the two membranes, the virus carries a protein called hemagglutinin (the "H" in H1N1). Triggered by the acidic environment of an endosome, that protein will extend from the viral membrane and attach, like a grappling hook, to the endosome's membrane. When enough hooks are set, they draw the membranes together until they fuse The flu virus carries about 300 to 400 of these hooks, and virologists had known that several are needed to fuse the membranes.

 

In their latest study, reported last month in the new journal eLife, the HMS team show why. Using a microscope developed by first author Tijana Ivanovic, a research fellow in the HMS Department of Biological Chemistry and Molecular Pharmacology, the team looked closely at changes in the protein throughout its assault on the endosome. They observed that three or four hemagluttinin hooks must attach in close proximity to fuse the membranes. Without the help of neighbors, an individual hook is too weak to pull the membranes together. Instead, they observed, the protein remains stretched between the two membranes, like a bridge. And that's an intriguing target, said Stephen Harrison, the study's senior author and the Giovanni Armenise-Harvard Professor of Basic Biomedical Science in the department of Biological Chemistry and Molecular Pharmacology at HMS. "That bridge can hang out there for as long as a minute," Harrison said. "That makes it an interesting target for an inhibitor, in principle, at least, because it's there for long enough to be targetable." The study also appears to settle a question about the nature of the hemagglutinin protein, and viral fusion: Are multiple hooks needed because they interact directly with each other to fuse the membranes, or because that's the number required to pull the somewhat elastic membranes together by brute force? The researchers' answer: brute force. "That observation helps us distinguish between classes of models for a stage of the fusion process," Harrison said. "That notion is probably fundamental to all viral fusion proteins—or for that matter to most cellular membrane fusion events facilitated by proteins."


Via Dr. Stefan Gruenwald, burkesquires
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Influenza
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Viral evolution: Past, present and future of influenza viruses : Nature Reviews Microbiology : Nature Publishing Group

Viral evolution: Past, present and future of influenza viruses : Nature Reviews Microbiology : Nature Publishing Group | Influenza | Scoop.it
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Avian Flu Diary: Novel H5N1 Reassortment Detected In Migratory Birds - China

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Avian Flu Diary: Eurosurveillance: Parotitis Associated With A Drifted A/H3N2 Infection

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Avian Flu Diary: JMII: Epidemiology Of Human Influenza A(H7N9) Infection In Hong Kong

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Avian Flu Diary: Defra: Preliminary Analysis Of Germany’s HPAI H7N7 Outbreak

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Avian Flu Diary: EID Journal: Infection Risk To Those Exposed To HPAI H5 Viruses – United States

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Avian Flu Diary: Referral: McKenna On the Costs Of HPAI H5 (Past & Future) In North America

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Avian Flu Diary: CDC Expert Commentary (Video) On Use Of Neuraminidase Antiviral Drugs

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Human infection with avian influenza A(H7N9) virus – China - World Health Organization

On 12 June 2015, the National Health and Family Planning Commission (NHFPC) of China notified WHO of 15 additional laboratory-confirmed cases of human infection with avian influenza A (H7N9) virus, including 3 deaths.
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A case report of avian influenza H7N9 killing a young doctor in Shanghai, China - BMC Blogs Network

The novel avian influenza H7N9 virus has caused severe diseases in humans in eastern China since the spring of 2013. On January 18 th 2014, a doctor working in the emergency department of a hospital in...
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Ahead of Print -Influenza A Viruses of Human Origin in Swine, Brazil - Volume 21, Number 8—August 2015 - Emerging Infectious Disease journal - CDC

Ahead of Print -Influenza A Viruses of Human Origin in Swine, Brazil - Volume 21, Number 8—August 2015 - Emerging Infectious Disease journal - CDC | Influenza | Scoop.it
The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.
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Avian Flu Diary: Avian Path: Susceptibility of Wild Passerine Birds To HPAI H5N1

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Avian Flu Diary: Eurosurveillance: Seroprevalence Of Cross-Reactive Antibodies To Swine H3N2v – Germany

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Avian Flu Diary: Eurosurveillance: B/Victoria Prevalence In Early New South Wales Flu Season

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Avian Flu Diary: JID: Evolutionary Dynamics Of Influenza A Viruses In US Exhibition Swine

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Avian Flu Diary: PLoS One: Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin

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Avian Flu Diary: CDC Study: Pathogenesis & Transmissibility Of HPAI H5 In Mice & Ferrets

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Avian Flu Diary: JAMA: Immune Response Of H7N9 Vaccine With & Without Adjuvant

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Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014–2015 Influenza Season: Cell Reports

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Viral evolution Global patterns of influenza circulation - Nature.com

Medical News Today
Viral evolution Global patterns of influenza circulation
Nature.com
Understanding the factors that influence the circulation of seasonal influenza viruses is a major public health challenge.
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BiondVax Announces FDA Acceptance of IND Application for Investigational Flu Vaccine

This IND continues BiondVax's clinical program, and will allow BiondVax to conduct an FDA approved Phase 2 clinical trial that will involve the administration of M-001, BiondVax's product candidate.
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Characteristics of oseltamivir-resistant influenza A (H1N1) pdm09 virus during the 2013–2014 influenza season in Mainland China

Background: In this study, we analyzed the characteristics of oseltamivir-resistant influenza A (H1N1) pdm09 virus isolated from patients in mainland China during the influenza season from September 2013 through March 2014, and provide guidance on...
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Avian Flu Diary: AAC: LPAI H7N9 Acquires Antiviral Resistance When Exposed To Environmental Oseltamivir

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