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Influenza
Flu in all Forms, Be Informed...Not Panicked.
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Rescooped by Mel Melendrez-Vallard from Virology and Bioinformatics from Virology.ca
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Structural insight into cap-snatching and RNA synthesis by influenza polymerase : Nature

Influenza virus polymerase uses a capped primer, derived by ‘cap-snatching’ from host pre-messenger RNA, to transcribe its RNA genome into mRNA and a stuttering mechanism to generate the poly(A) tail. By contrast, genome replication is unprimed and generates exact full-length copies of the template. Here we use crystal structures of bat influenza A and human influenza B polymerases (FluA and FluB), bound to the viral RNA promoter, to give mechanistic insight into these distinct processes. In the FluA structure, a loop analogous to the priming loop of flavivirus polymerases suggests that influenza could initiate unprimed template replication by a similar mechanism. Comparing the FluA and FluB structures suggests that cap-snatching involves in siturotation of the PB2 cap-binding domain to direct the capped primer first towards the endonuclease and then into the polymerase active site. The polymerase probably undergoes considerable conformational changes to convert the observed pre-initiation state into the active initiation and elongation states.


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Rescooped by Mel Melendrez-Vallard from Computational biology
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Mutations associated with severity of the pandemic influenza A(H1N1)pdm09 in humans: a systematic review and meta-analysis of epidemiological evidence - Arch Virol. 2014

Abstract

Mutations in the haemagglutinin (HA), non-structural protein 1 (NS1) and polymerase basic protein 2 (PB2) of influenza viruses have been associated with virulence. This study investigated the association between mutations in these genes in influenza A(H1N1)pdm09 virus and the risk of severe or fatal disease. Searches were conducted on the MEDLINE, EMBASE and Web of Science electronic databases and the reference lists of published studies. The PRISMA and STROBE guidelines were followed in assessing the quality of studies and writing-up. Eighteen (18) studies, from all continents, were included in the systematic review (recruiting patients 0 - 77 years old). The mutation D222G was associated with a significant increase in severe disease (pooled RD: 11 %, 95 % CI: 3.0 % - 18.0 %, p = 0.004) and the risk of fatality (RD: 23 %, 95 % CI: 14.0 %-31.0 %, p = < 0.0001). No association was observed between the mutations HA-D222N, D222E, PB2-E627K and NS1-T123V and severe/fatal disease. The results suggest that no virus quasispecies bearing virulence-conferring mutations in the HA, PB2 and NS1 predominated. However issues of sampling bias, and bias due to uncontrolled confounders such as comorbidities, and viral and bacterial coinfection, should be born in mind. Influenza A viruses should continue to be monitored for the occurrence of virulence-conferring mutations in HA, PB2 and NS1. There are suggestions that respiratory virus coinfections also affect virus virulence. Studies investigating the role of genetic mutations on disease outcome should make efforts to also investigate the role of respiratory virus coinfections.


Via burkesquires, Asela Wijeratne
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Rescooped by Mel Melendrez-Vallard from Virology and Bioinformatics from Virology.ca
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Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution

Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution | Influenza | Scoop.it

Influenza A virus has evolved and thrived in human populations. Since the 1918 influenza A pandemic, human H1N1 viruses had acquired additional N-linked glycosylation (NLG) sites within the globular head region of hemagglutinin (HA) until the NLG-free HA head pattern of the 1918 H1N1 virus was renewed with the swine-derived 2009 pandemic H1N1 virus. Moreover, the HA of the 2009 H1N1 virus appeared to be antigenically related to that of the 1918 H1N1 virus.


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Rescooped by Mel Melendrez-Vallard from Virology News
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What Do We Know About the New Bird Flu?

What Do We Know About the New Bird Flu? | Influenza | Scoop.it

Water birds, to an influenza researcher, are more than majestic swans and charming mallards.  They are instead stealthy vectors of novel influenza viruses, some of nature’s bioterrorist agents, chauffeuring dangerous microbes from place to place without showing symptoms of infection themselves. Wild waterfowl are reservoirs for every imaginable combination of influenza viruses, though the vast majority of those viral cocktails don’t seem to infect humans.


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Ed Rybicki's curator insight, April 11, 2013 9:28 AM

ALL birds are winged rats, then??  I love the actual title of the piece: "Nature’s Bioterrorist Agents".  Not alarming in any way, oh, no....

Rescooped by Mel Melendrez-Vallard from Virology News
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A Brief History of Influenza

A Brief History of Influenza | Influenza | Scoop.it
I am TRYING to write an eBook on influenza, which stubbornly refuses to be finished - as part of a sabbatical project, which finished in December 2010.  So, like my History of Virology, I am triall...

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Ed Rybicki's curator insight, April 5, 2013 5:15 AM

I will reprise this post, given a considerable recent spike in interest in it as the new H7N9 Shanghai bird flu starts.  Hopefully to fizzle out, but you never know....

 

Incidentally, I have an almost-finished iBook (for iPad) on influenza: the first five respondents to this post can trial it for free!

Chris Upton + helpers's comment, April 8, 2013 2:39 PM
cool... and I have iPad
Rescooped by Mel Melendrez-Vallard from Virology and Bioinformatics from Virology.ca
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Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding

Abstract

As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.


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Rescooped by Mel Melendrez-Vallard from Virology and Bioinformatics from Virology.ca
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BMC Medicine | Abstract | Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis

Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains.

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Mel Melendrez-Vallard's curator insight, June 27, 2013 7:21 PM

a good way to 'catch up'

Rescooped by Mel Melendrez-Vallard from Virology News
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Mississauga Article: Making vaccine for new bird flu virus could be a challenge

Mississauga Article: Making vaccine for new bird flu virus could be a challenge | Influenza | Scoop.it
TORONTO — Making a vaccine to protect against the new bird flu virus that has emerged in eastern China could prove to be problematic, influenza experts acknowledged yesterday.

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Ed Rybicki's curator insight, April 12, 2013 9:17 AM

"...clinical trials of vaccines made to protect against other viruses in the H7 family have shown the vaccines don't induce much of an immune response, even when people are given what would be considered very large doses."


This is a little worrying - and possibly a spur to making universal vaccines!

Rescooped by Mel Melendrez-Vallard from Virology News
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GlaxoSmithKline’s quadrivalent influenza vaccine approved in UK and Germany

GlaxoSmithKline’s quadrivalent influenza vaccine approved in UK and Germany | Influenza | Scoop.it

GlaxoSmithKline’s quadrivalent influenza vaccine has been granted marketing authorisation in Germany and the UK. The four-strain vaccine is the first  to be approved in a European country for active immunisation of adults and children from three years of age for the prevention of influenza disease caused by the two influenza A and two influenza B virus subtypes contained within the vaccine.


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