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Genetic Characterization of Highly Pathogenic Avian Influenza (H5N8) Virus from Domestic Ducks, England, November 2014

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      Abstract

      Genetic sequences of a highly pathogenic avian influenza (H5N8) virus in England have high homology to those detected in mainland Europe and Asia during 2014. Genetic characterization suggests this virus is an avian-adapted virus without specific affinity for zoonoses. Spatio-temporal detections of H5N8 imply a role for wild birds in virus spread.

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      Most cited references 8

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      MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.

      We announce the release of an advanced version of the Molecular Evolutionary Genetics Analysis (MEGA) software, which currently contains facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis. In version 6.0, MEGA now enables the inference of timetrees, as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny. A new Timetree Wizard in MEGA6 facilitates this timetree inference by providing a graphical user interface (GUI) to specify the phylogeny and calibration constraints step-by-step. This version also contains enhanced algorithms to search for the optimal trees under evolutionary criteria and implements a more advanced memory management that can double the size of sequence data sets to which MEGA can be applied. Both GUI and command-line versions of MEGA6 can be downloaded from www.megasoftware.net free of charge.
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        Airborne transmission of influenza A/H5N1 virus between ferrets.

        Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.
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          Experimental adaptation of an influenza H5 haemagglutinin (HA) confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

          Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host range determinant since it mediates virus binding to host-specific cellular receptors 1–3 . Here, we therefore assessed the molecular changes in HA that would allow an H5 HA-possessing virus to transmit among mammals. We identified a reassortant virus with H5 HA possessing four mutations in a 2009 pandemic H1N1 virus backbone capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but it was not highly pathogenic and did not cause mortality. These results suggest that H5 HA can convert to an HA that supports efficient viral transmission in mammals. However, we do not know whether the four mutations in the H5 HA identified in this study would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral genes may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need for pandemic preparedness for H5 HA-possessing viruses and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production, and distribution of effective countermeasures.
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            Author and article information

            Affiliations
            Animal and Plant Health Agency, Addlestone, UK
            Author notes
            Address for correspondence: Amanda Hanna, Virology, Animal and Plant Health Agency (APHA-Weybridge), Woodham Lane, Addlestone, Surrey, KT15 3NB, UK; email: Amanda.Hanna@ 123456apha.gsi.gov.uk
            Journal
            Emerg Infect Dis
            Emerging Infect. Dis
            EID
            Emerging Infectious Diseases
            Centers for Disease Control and Prevention
            1080-6040
            1080-6059
            May 2015
            : 21
            : 5
            : 879-882
            25898126
            4412239
            14-1954
            10.3201/eid2105.141954
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            Genetic Characterization of Highly Pathogenic Avian Influenza (H5N8) Virus from Domestic Ducks, England, November 2014

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