A Single Amino Acid in the HA of pH1N1 2009 Influenza Virus Affects Cell Tropism in Human Airway Epithelium, but Not Transmission in Ferrets
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{"title"=>"A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets", "type"=>"journal", "authors"=>[{"first_name"=>"Neeltje", "last_name"=>"van Doremalen", "scopus_author_id"=>"36009447200"}, {"first_name"=>"Holly", "last_name"=>"Shelton", "scopus_author_id"=>"8243087700"}, {"first_name"=>"Kim L.", "last_name"=>"Roberts", "scopus_author_id"=>"12809634600"}, {"first_name"=>"Ian M.", "last_name"=>"Jones", "scopus_author_id"=>"34769538800"}, {"first_name"=>"Ray J.", "last_name"=>"Pickles", "scopus_author_id"=>"7004225327"}, {"first_name"=>"Catherine I.", "last_name"=>"Thompson", "scopus_author_id"=>"37087933700"}, {"first_name"=>"Wendy S.", "last_name"=>"Barclay", "scopus_author_id"=>"7005440974"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"80053604087", "pmid"=>"21998692", "doi"=>"10.1371/journal.pone.0025755", "pui"=>"362707059", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "scopus"=>"2-s2.0-80053604087"}, "id"=>"d9668710-a333-39b7-9910-107817cf9715", "abstract"=>"The first pandemic of the 21(st) century, pandemic H1N1 2009 (pH1N1 2009), emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA) protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.", "link"=>"http://www.mendeley.com/research/single-amino-acid-ha-ph1n1-2009-influenza-virus-affects-cell-tropism-human-airway-epithelium-not-tra", "reader_count"=>33, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Ph. D. Student"=>9, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Ph. D. Student"=>9, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>4, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/727640"], "description"=>"<p>Presence of alanine, glutamic acid and other amino acids at position 227 in 173 full-length HA sequences of pre 2009 North-American swine H1 influenza.</p>", "links"=>[], "tags"=>["amino", "acids", "227", "swine", "h1"], "article_id"=>397994, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_amino_acids_at_position_227_in_swine_H1_Has_/397994", "title"=>"Distribution of amino acids at position 227 in swine H1 Has.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:13:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/728082"], "description"=>"<p>Viral titres in nasal wash samples of ferret pairs, each pair contained one donor (solid lines) and one respiratory droplet (dotted lines). Donors were inoculated with 10<sup>3</sup> PFU E195. Samples were taken daily and viral titres were determined by standard plaque assay on MDCK cells.</p>", "links"=>[], "tags"=>["e195", "ferrets", "respiratory", "droplet"], "article_id"=>398435, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transmission_of_wild_type_E195_in_ferrets_in_respiratory_droplet_sentinels_/398435", "title"=>"Transmission of wild type E195 in ferrets in respiratory droplet sentinels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/727963"], "description"=>"<p>Comparison of multi-cycle virus growth in MDCK cells or HAE cultures inoculated at MOI of 0.001 with isogenic viruses based on the E195 genetic backbone but with different HA proteins; either E195, E195 E227A or Ohio01 HA. Viral titres were determined by standard plaque assay on MDCK cells. Data shown represent the mean titre and standard deviation of 3 cultures. Statistical differences between wild type E195 and E195 E227A or Ohio01 were determined using one-way ANOVA. *  =  p<0.05, **  =  p<0.01.</p>", "links"=>[], "tags"=>["e227a", "ohio01", "attenuated", "hae"], "article_id"=>398315, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_E195_E227A_and_Ohio01_are_attenuated_in_HAE_cultures_/398315", "title"=>"E195 E227A and Ohio01 are attenuated in HAE cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:18:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/728351"], "description"=>"<p>Duration of shedding, peak titre and AUC were compared between ferrets directly inoculated or infected by respiratory droplet contact with wild type E195 or E195 E227A. Averages are displayed in bold with standard deviation indicated in brackets. The shedding parameters from ferrets infected by each virus were not significantly different as determined by Student's t-test.</p>", "links"=>[], "tags"=>["shedding", "inoculated", "respiratory", "droplet"], "article_id"=>398702, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.t002", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_virus_shedding_from_inoculated_and_respiratory_droplet_contact_animals_/398702", "title"=>"Summary of virus shedding from inoculated and respiratory droplet contact animals.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-05 02:25:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/727786"], "description"=>"<p>a/c/e) HAE culture sections were probed with HA-Fc proteins from human or swine H1N1 influenza virus strains. Ciliated cells were identified using anti-acetylated α-tubulin (red), and the HA-Fc proteins were visualized with anti-human Fc (green). Images are representative of multiple probed sections. Both non-ciliated cells (white arrow) and ciliated cells (yellow arrow) were present on human airway epithelium sections. b/d/f) HAE cultures were infected with MOI of 0.1 for 16 hrs. with isogenic viruses containing the HA genes of E195, E195 E227A or Ohio01. Ciliated cells were identified using anti-acetylated α-tubulin (red) and infected cells were detected with anti-NP antibody (green). Images are representative of multiple probed sections. Both non-ciliated cells (white arrow) and ciliated cells (yellow arrow) were present on human airway epithelium sections. g-h) Cell tropism was quantified by blind counting >200 cells per sample and expressed as the ratio of non-ciliated to ciliated cells bound or infected.</p>", "links"=>[], "tags"=>["shows", "tropism", "non-ciliated", "cells", "compared", "e195", "e227a", "ohio01", "hae"], "article_id"=>398123, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_E195_shows_a_tropism_preference_for_non_ciliated_cells_compared_to_E195_E227A_and_Ohio01_on_HAE_cultures_/398123", "title"=>"E195 shows a tropism preference for non-ciliated cells compared to E195 E227A and Ohio01 on HAE cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:15:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/728300"], "description"=>"<p>Sequence comparison of amino acid 227 and 219 (H3 numbering) of HA protein of H1N1 viruses, showing prototypic examples of seasonal H1N1, pH1N1 2009, classical swine influenza and dead-end zoonoses from swine to humans.</p>", "links"=>[], "tags"=>["227", "h1n1", "influenza", "human-to-human"], "article_id"=>398649, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Glutamic_acid_at_position_227_in_H1N1_influenza_virus_is_associated_with_human_to_human_transmission_/398649", "title"=>"Glutamic acid at position 227 in H1N1 influenza virus is associated with human-to-human transmission.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-05 02:24:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/728222"], "description"=>"<p>Viral titres in nasal wash samples of ferret sets, each pair contained one donor (solid lines) and one respiratory droplet (dotted lines). Donors were inoculated with 10<sup>4</sup> PFU E195 E227A. Samples were taken daily and viral titres were determined by standard plaque assay on MDCK cells.</p>", "links"=>[], "tags"=>["e195", "e227a", "respiratory", "droplet"], "article_id"=>398570, "categories"=>["Microbiology", "Virology", "Infectious Diseases"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transmission_of_E195_E227A_in_contact_and_respiratory_droplet_sentinels_/398570", "title"=>"Transmission of E195 E227A in contact and respiratory droplet sentinels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:22:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/367789"], "description"=>"<div><p>The first pandemic of the 21<sup>st</sup> century, pandemic H1N1 2009 (pH1N1 2009), emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA) protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.</p> </div>", "links"=>[], "tags"=>["amino", "ph1n1", "2009", "influenza", "affects", "tropism", "airway", "ferrets"], "article_id"=>132662, "categories"=>["Cancer", "Microbiology"], "users"=>["Neeltje van Doremalen", "Holly Shelton", "Kim L. Roberts", "Ian M. Jones", "Ray J. Pickles", "Catherine I. Thompson", "Wendy S. Barclay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025755", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Single_Amino_Acid_in_the_HA_of_pH1N1_2009_Influenza_Virus_Affects_Cell_Tropism_in_Human_Airway_Epithelium_but_Not_Transmission_in_Ferrets/132662", "title"=>"A Single Amino Acid in the HA of pH1N1 2009 Influenza Virus Affects Cell Tropism in Human Airway Epithelium, but Not Transmission in Ferrets", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 00:44:22"}

PMC Usage Stats | Further Information

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Relative Metric

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