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      • Record: found
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      A peptide-based approach to evaluate the adaptability of influenza A virus to humans based on its hemagglutinin proteolytic cleavage site

      research-article
      Author(s): 1 , 2 , 1 , 2 , *
      Editor(s):
      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Cleavage activation of the hemagglutinin (HA) protein by host proteases is a crucial step in the infection process of influenza A viruses (IAV). However, IAV exists in eighteen different HA subtypes in nature and their cleavage sites vary considerably. There is uncertainty regarding which specific proteases activate a given HA in the human respiratory tract. Understanding the relationship between different HA subtypes and human-specific proteases will be valuable in assessing the pandemic potential of circulating viruses. Here we utilized fluorogenic peptides mimicking the HA cleavage motif of representative IAV strains causing disease in humans or of zoonotic/pandemic potential and tested them with a range of proteases known to be present in the human respiratory tract. Our results show that peptides from the H1, H2 and H3 subtypes are cleaved efficiently by a wide range of proteases including trypsin, matriptase, human airway tryptase (HAT), kallikrein-related peptidases 5 (KLK5) and 12 (KLK12) and plasmin. Regarding IAVs currently of concern for human adaptation, cleavage site peptides from H10 viruses showed very limited cleavage by respiratory tract proteases. Peptide mimics from H6 viruses showed broader cleavage by respiratory tract proteases, while H5, H7 and H9 subtypes showed variable cleavage; particularly matriptase appeared to be a key protease capable of activating IAVs. We also tested HA substrate specificity of Factor Xa, a protease required for HA cleavage in chicken embryos and relevant for influenza virus production in eggs. Overall our data provide novel tool allowing the assessment of human adaptation of IAV HA subtypes.

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          Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

          Rongbao Gao, Bin Cao, Yunwen Hu … (2013)
          New England Journal of Medicine, 368(20), 1888-1897
          Article 0 comments Cited 1001 times – based on 0 reviews     Review now
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            1918 Influenza: the Mother of All Pandemics

            Jeffery K Taubenberger, David M. Morens (2006)
            The "Spanish" influenza pandemic of 1918–1919, which caused ≈50 million deaths worldwide, remains an ominous warning to public health. Many questions about its origins, its unusual epidemiologic features, and the basis of its pathogenicity remain unanswered. The public health implications of the pandemic therefore remain in doubt even as we now grapple with the feared emergence of a pandemic caused by H5N1 or other virus. However, new information about the 1918 virus is emerging, for example, sequencing of the entire genome from archival autopsy tissues. But, the viral genome alone is unlikely to provide answers to some critical questions. Understanding the 1918 pandemic and its implications for future pandemics requires careful experimentation and in-depth historical analysis.
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              Avian influenza A (H5N1) infection in humans.

              John H Beigel, Jeremy Farrar, Aye Han … (2005)
              Article 0 comments Cited 439 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Charles J. Russell: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 30 March 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 3
                Electronic Location Identifier: e0174827
                Affiliations
                [1 ]Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
                [2 ]New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester, New York, United States of America
                St. Jude Children's Research Hospital, UNITED STATES
                Author notes

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

                • Conceptualization: GRW.

                • Data curation: MRS.

                • Funding acquisition: GRW.

                • Investigation: MRS.

                • Methodology: GRW MRS.

                • Project administration: GRW MRS.

                • Resources: GRW.

                • Supervision: GRW.

                • Validation: GRW MRS.

                • Visualization: MRS.

                • Writing – original draft: MRS GRW.

                • Writing – review & editing: MRS GRW.

                Article
                Publisher ID: PONE-D-17-01570
                DOI: 10.1371/journal.pone.0174827
                PMC ID: 5373629
                PubMed ID: 28358853
                SO-VID: 438f3fee-d8a0-460d-ab08-14c78d303993
                Copyright © © 2017 Straus, Whittaker
                License:

                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
                Date received : 12 January 2017
                Date accepted : 15 March 2017
                Page count
                Figures: 7, Tables: 1, Pages: 17
                Funding
                Funded by: CEIRS
                Award ID: HHSN272201400005C
                Award Recipient :
                This work was funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under the Centers of Excellence for Influenza Research and Surveillance (CEIRS) Contract No. HHSN272201400005C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Enzymology
                Subject: Enzymes
                Subject: Proteases
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: Enzymes
                Subject: Proteases
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: Biology and life sciences
                Subject: Microbiology
                Subject: Medical microbiology
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: Medicine and health sciences
                Subject: Pathology and laboratory medicine
                Subject: Pathogens
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Peptides
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H5N1
                Subject: Biology and life sciences
                Subject: Microbiology
                Subject: Medical microbiology
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H5N1
                Subject: Medicine and health sciences
                Subject: Pathology and laboratory medicine
                Subject: Pathogens
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H5N1
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H5N1
                Subject: Medicine and Health Sciences
                Subject: Infectious Diseases
                Subject: Zoonoses
                Subject: H5N1
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H1N1
                Subject: Biology and life sciences
                Subject: Microbiology
                Subject: Medical microbiology
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H1N1
                Subject: Medicine and health sciences
                Subject: Pathology and laboratory medicine
                Subject: Pathogens
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H1N1
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H1N1
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Enzymology
                Subject: Enzymes
                Subject: Proteases
                Subject: Serine Proteases
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: Enzymes
                Subject: Proteases
                Subject: Serine Proteases
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Enzymology
                Subject: Enzymes
                Subject: Plasmins
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: Enzymes
                Subject: Plasmins
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H7N9
                Subject: Biology and life sciences
                Subject: Microbiology
                Subject: Medical microbiology
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H7N9
                Subject: Medicine and health sciences
                Subject: Pathology and laboratory medicine
                Subject: Pathogens
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H7N9
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral pathogens
                Subject: Orthomyxoviruses
                Subject: Influenza viruses
                Subject: Influenza A virus
                Subject: H7N9
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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