25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Avian Influenza Virus H3 Hemagglutinin May Enable High Fitness of Novel Human Virus Reassortants

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Reassortment of influenza A virus genes enables antigenic shift resulting in the emergence of pandemic viruses with novel hemagglutinins (HA) acquired from avian strains. Here, we investigated whether historic and contemporary avian strains with different replication capacity in human cells can donate their hemagglutinin to a pandemic human virus. We performed double-infections with two avian H3 strains as HA donors and a human acceptor strain, and determined gene compositions and replication of HA reassortants in mammalian cells. To enforce selection for the avian virus HA, we generated a strictly elastase-dependent HA cleavage site mutant from A/Hong Kong/1/68 (H3N2) (Hk68-Ela). This mutant was used for co-infections of human cells with A/Duck/Ukraine/1/63 (H3N8) (DkUkr63) or the more recent A/Mallard/Germany/Wv64-67/05 (H3N2) (MallGer05) in the absence of elastase but presence of trypsin. Among 21 plaques analyzed from each assay, we found 12 HA reassortants with DkUkr63 (4 genotypes) and 14 with MallGer05 (10 genotypes) that replicated in human cells comparable to the parental human virus. Although DkUkr63 replicated in mammalian cells at a reduced level compared to MallGer05 and Hk68, it transmitted its HA to the human virus, indicating that lower replication efficiency of an avian virus in a mammalian host may not constrain the emergence of viable HA reassortants. The finding that HA and HA/NA reassortants replicated efficiently like the human virus suggests that further HA adaptation remains a relevant barrier for emergence of novel HA reassortants.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: not found

          Emergence and pandemic potential of swine-origin H1N1 influenza virus.

          Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Avian flu: influenza virus receptors in the human airway.

            Although more than 100 people have been infected by H5N1 influenza A viruses, human-to-human transmission is rare. What are the molecular barriers limiting human-to-human transmission? Here we demonstrate an anatomical difference in the distribution in the human airway of the different binding molecules preferred by the avian and human influenza viruses. The respective molecules are sialic acid linked to galactose by an alpha-2,3 linkage (SAalpha2,3Gal) and by an alpha-2,6 linkage (SAalpha2,6Gal). Our findings may provide a rational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficiently in the lungs.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A single amino acid in the PB2 gene of influenza A virus is a determinant of host range.

              The single gene reassortant virus that derives its PB2 gene from the avian influenza A/Mallard/NY/78 virus and remaining genes from the human influenza A/Los Angeles/2/87 virus exhibits a host range restriction (hr) phenotype characterized by efficient replication in avian tissue and failure to produce plaques in mammalian Madin-Darby canine kidney cells. The hr phenotype is associated with restriction of viral replication in the respiratory tract of squirrel monkeys and humans. To identify the genetic basis of the hr phenotype, we isolated four phenotypic hr mutant viruses that acquired the ability to replicate efficiently in mammalian tissue. Segregational analysis indicated that the loss of the hr phenotype was due to a mutation in the PB2 gene itself. The nucleotide sequences of the PB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu-->Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells. Interestingly, the amino acid at position 627 in every avian influenza A virus PB2 protein analyzed to date is glutamic acid, and in every human influenza A virus PB2 protein, it is lysine. Thus, the amino acid at residue 627 of PB2 is an important determinant of host range of influenza A viruses.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                12 November 2013
                : 8
                : 11
                : e79165
                Affiliations
                [1 ]Friedrich-Loeffler-Institut, Institute of Molecular Biology, Greifswald-Insel Riems, Germany
                [2 ]Friedrich-Loeffler-Institut, Biomathematics Working Group, Greifswald-Insel Riems, Germany
                University of Edinburgh, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: OS JS. Performed the experiments: AK JH OS. Analyzed the data: AK OS MZ JS. Contributed reagents/materials/analysis tools: JH OS. Wrote the paper: TCM JS.

                [¤a]

                Current address: Ecuphar GmbH, Greifswald, Germany

                [¤b]

                Current address: Calgary, Alberta, Canada

                Article
                PONE-D-13-04453
                10.1371/journal.pone.0079165
                3827155
                46f90345-1ddb-4402-a834-543d8caa442c
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 January 2013
                : 20 September 2013
                Page count
                Pages: 9
                Funding
                This work was supported by the Forschungssofortprogramm Influenza of the German Government (FSI 2.44). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article