Phenotypic Differences in Virulence and Immune Response in Closely Related Clinical Isolates of Influenza A 2009 H1N1 Pandemic Viruses in Mice
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{"title"=>"Phenotypic Differences in Virulence and Immune Response in Closely Related Clinical Isolates of Influenza A 2009 H1N1 Pandemic Viruses in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Jeremy V.", "last_name"=>"Camp", "scopus_author_id"=>"36109982300"}, {"first_name"=>"Yong Kyu", "last_name"=>"Chu", "scopus_author_id"=>"7403050776"}, {"first_name"=>"Dong Hoon", "last_name"=>"Chung", "scopus_author_id"=>"35073678300"}, {"first_name"=>"Ryan C.", "last_name"=>"McAllister", "scopus_author_id"=>"55602965400"}, {"first_name"=>"Robert S.", "last_name"=>"Adcock", "scopus_author_id"=>"55603363700"}, {"first_name"=>"Rachael L.", "last_name"=>"Gerlach", "scopus_author_id"=>"55603384200"}, {"first_name"=>"Timothy L.", "last_name"=>"Wiemken", "scopus_author_id"=>"35323168000"}, {"first_name"=>"Paula", "last_name"=>"Peyrani", "scopus_author_id"=>"16307950000"}, {"first_name"=>"Julio A.", "last_name"=>"Ramirez", "scopus_author_id"=>"35444694300"}, {"first_name"=>"James T.", "last_name"=>"Summersgill", "scopus_author_id"=>"7004302234"}, {"first_name"=>"Colleen B.", "last_name"=>"Jonsson", "scopus_author_id"=>"7102791844"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368381801", "sgr"=>"84874133494", "pmid"=>"23441208", "scopus"=>"2-s2.0-84874133494", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0056602", "issn"=>"19326203"}, "id"=>"3ab73ee3-4384-33d2-8752-6440d6aee49a", "abstract"=>"To capture the possible genotypic and phenotypic differences of the 2009 influenza A virus H1N1 pandemic (H1N1pdm) strains circulating in adult hospitalized patients, we isolated and sequenced nine H1N1pdm viruses from patients hospitalized during 2009-2010 with severe influenza pneumonia in Kentucky. Each viral isolate was characterized in mice along with two additional H1N1 pandemic strains and one seasonal strain to assess replication and virulence. All isolates showed similar levels of replication in nasal turbinates and lung, but varied in their ability to cause morbidity. Further differences were identified in cytokine and chemokine responses. IL-6 and KC were expressed early in mice infected with strains associated with higher virulence. Strains that showed lower pathogenicity in mice had greater IFNγ, MIG, and IL-10 responses. A principal component analysis (PCA) of the cytokine and chemokine profiles revealed 4 immune response phenotypes that correlated with the severity of disease. A/KY/180/10, which showed the greatest virulence with a rapid onset of disease progression, was compared in additional studies with A/KY/136/09, which showed low virulence in mice. Analyses comparing a low (KY/136) versus a high (KY/180) virulent isolate showed a significant difference in the kinetics of infection within the lower respiratory tract and immune responses. Notably by 4 DPI, virus titers within the lung, bronchoalveolar lavage fluid (BALf), and cells within the BAL (BALc) revealed that the KY/136 replicated in BALc, while KY/180 replication persisted in lungs and BALc. In summary, our studies suggest four phenotypic groups based on immune responses that result in different virulence outcomes in H1N1pdm isolates with a high degree of genetic similarity. In vitro studies with two of these isolates suggested that the more virulent isolate, KY/180, replicates productively in macrophages and this may be a key determinant in tipping the response toward a more severe disease progression.", "link"=>"http://www.mendeley.com/research/phenotypic-differences-virulence-immune-response-closely-related-clinical-isolates-influenza-2009-h1", "reader_count"=>13, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>5, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}}, "reader_count_by_country"=>{"China"=>1, "United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/486703", "https://ndownloader.figshare.com/files/486704", "https://ndownloader.figshare.com/files/486710", "https://ndownloader.figshare.com/files/486714", "https://ndownloader.figshare.com/files/486715", "https://ndownloader.figshare.com/files/486720", "https://ndownloader.figshare.com/files/486724", "https://ndownloader.figshare.com/files/486727", "https://ndownloader.figshare.com/files/486731", "https://ndownloader.figshare.com/files/486735", "https://ndownloader.figshare.com/files/486740", "https://ndownloader.figshare.com/files/486745", "https://ndownloader.figshare.com/files/486747"], "description"=>"<div><p>To capture the possible genotypic and phenotypic differences of the 2009 influenza A virus H1N1 pandemic (H1N1pdm) strains circulating in adult hospitalized patients, we isolated and sequenced nine H1N1pdm viruses from patients hospitalized during 2009–2010 with severe influenza pneumonia in Kentucky. Each viral isolate was characterized in mice along with two additional H1N1 pandemic strains and one seasonal strain to assess replication and virulence. All isolates showed similar levels of replication in nasal turbinates and lung, but varied in their ability to cause morbidity. Further differences were identified in cytokine and chemokine responses. IL-6 and KC were expressed early in mice infected with strains associated with higher virulence. Strains that showed lower pathogenicity in mice had greater IFNγ, MIG, and IL-10 responses. A principal component analysis (PCA) of the cytokine and chemokine profiles revealed 4 immune response phenotypes that correlated with the severity of disease. A/KY/180/10, which showed the greatest virulence with a rapid onset of disease progression, was compared in additional studies with A/KY/136/09, which showed low virulence in mice. Analyses comparing a low (KY/136) versus a high (KY/180) virulent isolate showed a significant difference in the kinetics of infection within the lower respiratory tract and immune responses. Notably by 4 DPI, virus titers within the lung, bronchoalveolar lavage fluid (BALf), and cells within the BAL (BALc) revealed that the KY/136 replicated in BALc, while KY/180 replication persisted in lungs and BALc. In summary, our studies suggest four phenotypic groups based on immune responses that result in different virulence outcomes in H1N1pdm isolates with a high degree of genetic similarity. <i>In vitro</i> studies with two of these isolates suggested that the more virulent isolate, KY/180, replicates productively in macrophages and this may be a key determinant in tipping the response toward a more severe disease progression.</p> </div>", "links"=>[], "tags"=>["phenotypic", "differences", "virulence", "isolates", "influenza", "2009", "h1n1", "pandemic", "viruses", "mice"], "article_id"=>157311, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.s001", "https://dx.doi.org/10.1371/journal.pone.0056602.s002", "https://dx.doi.org/10.1371/journal.pone.0056602.s003", "https://dx.doi.org/10.1371/journal.pone.0056602.s004", "https://dx.doi.org/10.1371/journal.pone.0056602.s005", "https://dx.doi.org/10.1371/journal.pone.0056602.s006", "https://dx.doi.org/10.1371/journal.pone.0056602.s007", "https://dx.doi.org/10.1371/journal.pone.0056602.s008", "https://dx.doi.org/10.1371/journal.pone.0056602.s009", "https://dx.doi.org/10.1371/journal.pone.0056602.s010", "https://dx.doi.org/10.1371/journal.pone.0056602.s011", "https://dx.doi.org/10.1371/journal.pone.0056602.s012", "https://dx.doi.org/10.1371/journal.pone.0056602.s013"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Phenotypic_Differences_in_Virulence_and_Immune_Response_in_Closely_Related_Clinical_Isolates_of_Influenza_A_2009_H1N1_Pandemic_Viruses_in_Mice__/157311", "title"=>"Phenotypic Differences in Virulence and Immune Response in Closely Related Clinical Isolates of Influenza A 2009 H1N1 Pandemic Viruses in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-18 02:01:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/486926"], "description"=>"<p>Six to eight week old DBA/2 mice were infected intranasally with 10<sup>5</sup> TCID<sub>50</sub> with a seasonal virus isolate (BN/59), Kentucky (KY/80, KY/136, KY/96, KY/99, KY/104, KY/108, KY/108, KY/110, KY/180, KY/190) or other H1N1 pandemic isolates (CA/07, NY/18) from 2009. Cytokine levels were measured at 3 and 6 DPI as described in the materials and methods and presented as mean +/− SEM (n = 6 per group, although fewer animals were available for lethal isolates).</p>", "links"=>[], "tags"=>["levels", "mice", "infected", "pandemic", "seasonal", "h1n1", "influenza"], "article_id"=>157424, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_levels_in_mice_infected_with_pandemic_and_seasonal_H1N1_influenza_viruses_/157424", "title"=>"Cytokine levels in mice infected with pandemic and seasonal H1N1 influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:03:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/487018"], "description"=>"<p>Six to eight week old DBA/2 mice were infected intranasally with 10<sup>5</sup> TCID<sub>50</sub> with a seasonal virus isolate (BN/59), Kentucky (KY/80, KY/136, KY/96, KY/99, KY/104, KY/108, KY/108, KY/110, KY/180, KY/190) or other H1N1 pandemic isolates (CA/07, NY/18) from 2009. Chemokine levels were measured at 3 and 6 DPI as described in the materials and methods and presented as mean +/− SEM (n = 6 per group when possible).</p>", "links"=>[], "tags"=>["levels", "mice", "infected", "pandemic", "seasonal", "h1n1", "influenza"], "article_id"=>157526, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemokine_levels_in_mice_infected_with_pandemic_and_seasonal_H1N1_influenza_viruses_/157526", "title"=>"Chemokine levels in mice infected with pandemic and seasonal H1N1 influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:05:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/487137"], "description"=>"<p>A principal components analysis was performed using the 14 cytokines/chemokines analytes shown to be the most significantly different across all isolates from days 3 and 6 (determined by generalized linear model fitness testing, data not shown). The data were normalized and scaled (zero mean-centered) cytokine responses after influenza infection at 3 and 6 DPI for all viruses. The ordinate and abscissa represent the first and second components from the PCA, which explain approximately 72% of the variance. Each arrow represents the mean of a virus isolate tested in mice. Arrow tails represent day 3 components and arrow heads represent day 6 components. Using this tool to visualize the immune response, the arrows depict the trajectory of disease of the various influenza isolates as tested in DBA/2 mice. Additionally, the 12 virus isolates clustered into four distinct patterns: Group 1, BN/59, CA/07, KY/80, KY/136; Group 2, KY/96, KY/99, KY/104, KY/108; Group 3, KY/108, KY/110; Group 4, KY/180, KY/190, NY/18 (See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056602#pone.0056602.s012\" target=\"_blank\">Table S5</a>).</p>", "links"=>[], "tags"=>["components", "responses", "lungs", "mice", "pandemic", "seasonal", "influenza"], "article_id"=>157643, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Principal_components_analysis_of_immune_responses_in_lungs_of_mice_to_infection_with_pandemic_and_seasonal_influenza_viruses_/157643", "title"=>"Principal components analysis of immune responses in lungs of mice to infection with pandemic and seasonal influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:07:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/487241"], "description"=>"<p>Mean weight change (+/− SEM) after six to eight week old DBA/2 mice were infected intranasally with 10<sup>0</sup>, 10<sup>2</sup> and 10<sup>5</sup> TCID<sub>50</sub> with KY/136E (A) or KY/180E (B). Mice were examined daily for clinical signs and weighed (<i>n</i> = 10 mice per virus group). Kaplan-Meier Survival curves for these mice show KY/136E to have low lethality (C) compared to KY/180E (D).</p>", "links"=>[], "tags"=>["kaplan-meier", "mice", "infected"], "article_id"=>157752, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Weight_loss_and_Kaplan_Meier_curve_of_mice_infected_with_KY_136_and_KY_180_/157752", "title"=>"Weight loss and Kaplan-Meier curve of mice infected with KY/136 and KY/180.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:09:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/487313"], "description"=>"<p>The levels of notable cytokine responses are shown for 1, 3 and 5 DPI in six to eight week old DBA/2 mice that were infected intranasally with 10<sup>5</sup> TCID<sub>50</sub> of KY/180E or KY/136E (<i>n</i> = 10 mice per virus group per time point). Statistical significance was determined by day using Kruskal-Wallis test followed by pairwise Wilcoxon Rank Sum <i>post hoc</i> test with Holm’s adjustment for multiple comparisons. <i>P</i>-values <0.05 are indicated by the following method: “a” = KY/180 is significantly different from mock; “b” = KY/136 is significantly different from mock; “c” = KY/180 is significantly different from KY/136.</p>", "links"=>[], "tags"=>["levels", "mice", "infected"], "article_id"=>157829, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_levels_in_mice_infected_with_KY_136_or_KY_180_/157829", "title"=>"Cytokine levels in mice infected with KY/136 or KY/180.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:10:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/487478"], "description"=>"<p>The levels of notable chemokine responses are shown for 1, 3 and 5 DPI in six to eight week old DBA/2 mice that were infected intranasally with 10<sup>5</sup> TCID<sub>50</sub> of KY/180E or KY/136E (<i>n</i> = 10 mice per virus group per time point). Statistical significance was determined by day using Kruskal-Wallis test followed by pairwise Wilcoxon Rank Sum <i>post hoc</i> test with Holm’s adjustment for multiple comparisons. <i>P</i>-values <0.05 are indicated by the following method: “a” = KY/180 is significantly different from mock; “b” = KY/136 is significantly different from mock; “c” = KY/180 is significantly different from KY/136.</p>", "links"=>[], "tags"=>["levels", "mice", "infected"], "article_id"=>157989, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemokine_levels_in_mice_infected_with_KY_136_or_KY_180_/157989", "title"=>"Chemokine levels in mice infected with KY/136 or KY/180.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:13:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/487661"], "description"=>"<p>Serum from day 20 post-infection was taken from six to eight week old DBA/2 mice that were infected intranasally with 10<sup>0</sup>, 10<sup>2</sup> and 10<sup>5</sup> TCID<sub>50</sub> of KY/180E or KY/136E (<i>n</i> = 10 mice per virus group per time point). Influenza-specific (A/NY/18/09 BPL-inactivated whole viral antigen) IgG titers were measured by ELISA and presented as average log<sub>2</sub> endpoint titers (+/−SEM). No mice survived to day 20 at the high dose of KY/180. All endpoint titers for animals infected with influenza virus isolates were significantly different from mock (<i>p</i><0.05). Endpoint titers for both IgG and HI from animals infected with KY/180 were significantly different from the same dosage amount of KY/136 (<i>p</i><0.05).</p>", "links"=>[], "tags"=>["responses", "mice", "infected", "doses"], "article_id"=>158165, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IgG_responses_of_mice_infected_with_different_doses_of_KY_136_or_KY_180_/158165", "title"=>"IgG responses of mice infected with different doses of KY/136 or KY/180.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:16:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/487792"], "description"=>"<p>The cells within the bronchoalveolar lavage fluid (BALf) at 4 DPI from DBA/2 mice infected with 10<sup>5</sup> TCID<sub>50</sub> of KY/136E (A) or KY/180E (B) (<i>n</i> = 5 mice per virus group per time point) were affixed to slides by cytospin centrifuge and stained (Kwik-Diff). Microscopic images from three fields per slide were counted by three blinded, independent observers. (C) The average number of macrophages, non-specific monocytes, and neutrophils are presented as a percent of the total cell count (+/− SEM). There were significantly more neutrophils in the BALf of mice infected with KY/180E virus (<i>p</i><0.05, indicated by asterisks). (D) Cells in the BALf were fixed, permeabilized, and stained with anti-influenza nucleoprotein (NP)-FITC antibody conjugate and analyzed by flow cytometry. There were significantly more NP-positive cells in mice infected with KY/180 at a dose of 10<sup>2</sup> pfu, and in mice infected with KY/136 compared to mock-infected controls (<i>p</i><0.05, indicated by asterisks). 80% of NP-positive cells were Gr-1 positive (macrophage or neutrophil).</p>", "links"=>[], "tags"=>["bronchial", "lavage", "mice", "infected"], "article_id"=>158300, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cells_within_bronchial_lavage_fluid_of_mice_infected_with_KY_136_or_KY_180_/158300", "title"=>"Cells within bronchial lavage fluid of mice infected with KY/136 or KY/180.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/487931"], "description"=>"<p>Bronchoalveolar lavage was taken from six to nine week old DBA/2 mice that were infected with 10<sup>5</sup> TCID<sub>50</sub> KY/136E or KY/180E on days 3 and 4 post-infection. Cells were separated from the lavage fluid by centrifugation and the fluid (BALf), cellular (BAL cell), and whole lung homogenate were tested separately for virus by TCID<sub>50</sub> assay on MDCK cells. Lung compartments taken from mice infected with KY/180 had statistically higher virus titers at 3 DPI than from mice infected with KY/136 (<i>p</i><0.05, indicated by asterisks on the figure). It is not possible to compute statistical differences from 4 DPI, as there were only two mice infected with KY/180 in that experiment that survived to 4 DPI.</p>", "links"=>[], "tags"=>["titer", "compartments", "mice", "infected"], "article_id"=>158437, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_titer_the_in_lung_compartments_of_mice_infected_with_KY_136_or_KY_180_/158437", "title"=>"Virus titer the in lung compartments of mice infected with KY/136 or KY/180.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:20:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/488093"], "description"=>"<p>Mouse macrophage cell line, RAW264.7, was infected <i>in vitro</i> with MOI = 1 of each influenza isolate (high pathogenic isolate, KY/180, and low pathogenic isolate, KY/136) on chambered microscopy slides. At 24 hours post-infection cells were fixed, permeabilized, and stained using a FITC antibody conjugate specific for influenza A (H1N1) nucleoprotein (green). Cells were counterstained with a nuclear dye (TO-PRO3, Molecular Probes, red), and visualized on a Zeiss LSM710 confocal microscope. Both isolates tested were observed to infect macrophages. Scale bars indicate 100 microns.</p>", "links"=>[], "tags"=>["influenza", "macrophage"], "article_id"=>158604, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g010"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_Influenza_in_mouse_macrophage_cell_lines_/158604", "title"=>"Detection of Influenza in mouse macrophage cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:23:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/488221"], "description"=>"<p>Mouse macrophage cell line, RAW264.7, was infected <i>in vitro</i> with the influenza isolates on a 24-well plate at an MOI = 1.0. After one hour of incubation, the cells were washed and returned to the incubator. Cell culture supernatants were collected over time and virus titer was determined by TCID<sub>50</sub> assay. Both KY/180E and KY/136E replicate in mouse macrophage cell lines. KY/180E had significantly higher titers of virus detected at 24 and 48 hours post-infection (<i>p</i><0.05, indicated by asterisks on the figure). Pathogenic isolate KY/180E was able to replicate better in mouse macrophages compared to the low pathogenic isolate, KY/136E.</p>", "links"=>[], "tags"=>["macrophage"], "article_id"=>158739, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.g011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_KY_180E_and_KY_136E_in_mouse_macrophage_cell_lines_/158739", "title"=>"Replication of KY/180E and KY/136E in mouse macrophage cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-18 02:25:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1004660"], "description"=>"*<p>locality, 2 = western Kentucky (KY); 3 = eastern KY; 6 = Louisville metro;</p>Ψ<p>LOS, Length of stay in hospital; MRSA, methicillin-Resistant <i>Staphylococcus aureus</i>; COPD, chronic obstructive pulmonary disease; BMI- body mass index; ND, none determined.</p>", "links"=>[], "tags"=>["nasal", "swabs"], "article_id"=>665279, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_General_Patient_Data_for_Nasal_Swabs_Used_for_Virus_Isolation_/665279", "title"=>"General Patient Data for Nasal Swabs Used for Virus Isolation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-18 01:27:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1004681"], "description"=>"<p>Legend: Virus titer (log10 TCID<sub>50</sub>/mL at a limit of detection = 10<sup>1.5</sup> TCID<sub>50</sub>/mL).</p>", "links"=>[], "tags"=>["viral", "lethality", "h1n1pdm", "isolates", "dba2"], "article_id"=>665299, "categories"=>["Microbiology", "Medicine", "Virology", "Infectious Diseases"], "users"=>["Jeremy V. Camp", "Yong-Kyu Chu", "Dong-Hoon Chung", "Ryan C. McAllister", "Robert S. Adcock", "Rachael L. Gerlach", "Timothy L. Wiemken", "Paula Peyrani", "Julio A. Ramirez", "James T. Summersgill", "Colleen B. Jonsson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056602.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_viral_titers_lethality_of_H1N1pdm_isolates_in_DBA2_mice_/665299", "title"=>"Summary of viral titers, lethality of H1N1pdm isolates in DBA2 mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-18 01:28:19"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"20", "full-text"=>"17", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"26", "supp-data"=>"40", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
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  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"6", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
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  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"24", "pdf"=>"1", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
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  • {"unique-ip"=>"20", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
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  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"29", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"4", "cited-by"=>"1", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
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Relative Metric

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