Extracellular HCV-Core Protein Induces an Immature Regulatory Phenotype in NK Cells: Implications for Outcome of Acute Infection
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{"title"=>"Extracellular HCV-core protein induces an immature regulatory phenotype in NK cells: Implications for outcome of acute infection", "type"=>"journal", "authors"=>[{"first_name"=>"Lucy", "last_name"=>"Golden-Mason", "scopus_author_id"=>"6603883641"}, {"first_name"=>"Young S.", "last_name"=>"Hahn", "scopus_author_id"=>"7101827236"}, {"first_name"=>"Michael", "last_name"=>"Strong", "scopus_author_id"=>"7101816695"}, {"first_name"=>"Linling", "last_name"=>"Cheng", "scopus_author_id"=>"15724371400"}, {"first_name"=>"Hugo R.", "last_name"=>"Rosen", "scopus_author_id"=>"7202726399"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373645974", "sgr"=>"84905054494", "issn"=>"19326203", "pmid"=>"25076408", "scopus"=>"2-s2.0-84905054494", "doi"=>"10.1371/journal.pone.0103219", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"a1277267-3f8f-33f6-aef1-d2b16ae25dc9", "abstract"=>"BACKGROUND: Hepatitis C viral (HCV) proteins, including core, demonstrate immuno-modulatory properties; however, the effect of extracellular core on natural killer (NK) cells has not previously been investigated. AIMS: To characterise NKs in acute HCV infection over time, and, to examine the effect of exogenous HCV-core protein on NK cell phenotype and function. METHODS: Acute HCV patients (n = 22), including 10 subjects who spontaneously recovered, were prospectively studied. Flow-cytometry was used to measure natural cytotoxicity and to phenotype NKs directly ex vivo and after culture with HCV-core protein. Microarray analysis was used to identify pathways involved in the NK cell response to exogenous HCV-core. RESULTS: Direct ex vivo analysis demonstrated an increased frequency of immature/regulatory CD56bright NKs early in acute HCV infection per se which normalized with viral clearance. Natural cytotoxicity was reduced and did not recover after viral clearance. There was a statistically significant correlation between the frequency of CD56bright NKs and circulating serum levels of HCV core protein. In vitro culture of purified CD56bright NK cells with HCV-core protein in the presence of IL-15 maintained a significant proportion of NKs in the CD56bright state. The in vitro effect of core closely correlates with NK characteristics measured directly ex vivo in acute HCV infection. Pathway analysis suggests that HCV-core protein attenuates NK interferon type I responses. CONCLUSIONS: Our data suggest that HCV-core protein alters NK cell maturation and may influence the outcome of acute infection.", "link"=>"http://www.mendeley.com/research/extracellular-hcvcore-protein-induces-immature-regulatory-phenotype-nk-cells-implications-outcome-ac", "reader_count"=>14, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>4, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>4, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>6, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}}, "reader_count_by_country"=>{"Japan"=>1, "South Africa"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1614792"], "description"=>"<p>Multi-parameter flow cytometric analysis was used to determine if the phenotype of NK cells was altered in acute HCV infection. Upregulation of Fas (<b>A</b>) and downregulation of Fas-Ligand (<b>B</b>) suggest activation of NK cells in acute HCV infection. Fas remains upregulated even after viral clearance. The decrease observed for NK CD16 expression in the chronically evolving patient group at month 6 (<b>C</b>) is consistent with altered NK subset distribution. Decreased expression of the inhibitory KIR CD158B (<b>D</b>) in the spontaneously resolving group at baseline suggests a genetic contribution to the outcome of acute HCV infection. * p<0.05 chronic versus resolved; † p<0.05 versus uninfected control (MWU) Abbreviations: NC = normal control; M = month.</p>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "nk", "cells", "acute", "hcv"], "article_id"=>1122189, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotype_of_NK_cells_in_acute_HCV_infection_/1122189", "title"=>"Phenotype of NK cells in acute HCV infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 03:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614796"], "description"=>"<p>Natural Cytotoxicity of bead-purified NK cells is compromised both early (M0) and late (M6) in acute HCV infection irrespective of outcome. * p<0.05 chronic versus resolved; † p<0.05 versus uninfected control (MWU) Abbreviations: NC = normal control; M = month.</p>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "competence", "nk", "cells", "acute", "hcv"], "article_id"=>1122193, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_competence_of_NK_cells_in_acute_HCV_infection_/1122193", "title"=>"Functional competence of NK cells in acute HCV infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 03:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614808"], "description"=>"<p>This network contains interconnections among 20 differentially expressed genes in response to HCV-core protein stimulation. Upregulated genes are indicated in green, and downregulated genes and gene classes in red. These differentially expressed genes include the cytotoxic T lymphocyte associated protein CTLA4, the cytochrome P450 proteins CYP2E1 and CYP3A4, the potassium voltage gated proteins KCNA1 and KCNB2, and the cell surface receptor CD200R1.</p>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "differentially"], "article_id"=>1122205, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Network_of_differentially_expressed_genes_/1122205", "title"=>"Network of differentially expressed genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 03:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614789"], "description"=>"<p><b>A)</b> Multi-parameter flow cytometric analysis was used to determine if the levels of peripheral NK cells (CD56<sup>+</sup>CD3<sup>-</sup>) were altered in acute HCV infection. <b>B)</b> Levels of total NK cells at time of enrollment and at six and twelve month follow up time points are similar to those detected in normal uninfected controls irrespective of subsequent clinical outcome. <b>C)</b> In contrast, an increase in the proportion of NK cells displaying a CD56<sup>bright</sup> immature/regulatory phenotype was observed at baseline in acute HCV infection <i>per se</i> with a trend that was more pronounced in chronically evolving infection compared to patients who subsequently resolved infection. The relatively high proportion of NK cells with an immature/regulatory phenotype was maintained in the chronically evolving cohort and returned to normal levels in the spontaneously resolving patient group at six and twelve months post enrollment. * p<0.05 chronic versus resolved; † p<0.05 versus uninfected control (MWU).</p>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "nk", "cells", "subset", "acute", "hcv"], "article_id"=>1122186, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequency_of_NK_cells_and_the_immature_regulatory_CD56_bright_subset_in_acute_HCV_infection_/1122186", "title"=>"Frequency of NK cells and the immature/regulatory CD56<sup>bright</sup> subset in acute HCV infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 03:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614802"], "description"=>"<p>Circulating HCV-core protein levels as measured by ELISA <b>(A)</b>. As expected, core levels correlated directly with viral levels in HCV-infected patients. There was also a direct statistically significant correlation between core and the levels of CD56<sup>bright</sup> NK cells in these patients. Multiple time points were used for chronic patients <b>(B)</b>. Incubation of highly purified FACS sorted CD56<sup>bright</sup> NK cells, from normal uninfected control subjects, in the presence of HCV-core or beta-galactosidase (β-Gal) control protein demonstrated inhibition of CD56 down-regulation by exogenous HCV-core protein. Histograms of CD56 expression levels after incubation are shown for four individual experiments <b>(C)</b>. The first three histograms represent individual normal control subjects and the fourth histogram is derived from an experiment in which PBMCs from five normal uninfected control subjects were pooled prior to sorting on CD56<sup>bright</sup> NK cells and incubation with HCV-core.</p>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "hcv-core", "acute", "hcv", "extracellular", "nk", "cd56"], "article_id"=>1122199, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Circulating_HCV_core_levels_in_acute_HCV_infection_and_effect_of_extracellular_core_on_NK_cell_CD56_expression_/1122199", "title"=>"Circulating HCV-core levels in acute HCV infection and effect of extracellular core on NK cell CD56 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 03:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614815"], "description"=>"<div><p>Background</p><p>Hepatitis C viral (HCV) proteins, including core, demonstrate immuno-modulatory properties; however, the effect of extracellular core on natural killer (NK) cells has not previously been investigated.</p><p>Aims</p><p>To characterise NKs in acute HCV infection over time, and, to examine the effect of exogenous HCV-core protein on NK cell phenotype and function.</p><p>Methods</p><p>Acute HCV patients (n = 22), including 10 subjects who spontaneously recovered, were prospectively studied. Flow-cytometry was used to measure natural cytotoxicity and to phenotype NKs directly <i>ex vivo</i> and after culture with HCV-core protein. Microarray analysis was used to identify pathways involved in the NK cell response to exogenous HCV-core.</p><p>Results</p><p>Direct <i>ex vivo</i> analysis demonstrated an increased frequency of immature/regulatory CD56<sup>bright</sup> NKs early in acute HCV infection <i>per se</i> which normalized with viral clearance. Natural cytotoxicity was reduced and did not recover after viral clearance. There was a statistically significant correlation between the frequency of CD56<sup>bright</sup> NKs and circulating serum levels of HCV core protein. <i>In vitro</i> culture of purified CD56<sup>bright</sup> NK cells with HCV-core protein in the presence of IL-15 maintained a significant proportion of NKs in the CD56<sup>bright</sup> state. The <i>in vitro</i> effect of core closely correlates with NK characteristics measured directly <i>ex vivo</i> in acute HCV infection. Pathway analysis suggests that HCV-core protein attenuates NK interferon type I responses.</p><p>Conclusions</p><p>Our data suggest that HCV-core protein alters NK cell maturation and may influence the outcome of acute infection.</p></div>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "hcv-core", "immature", "phenotype", "nk", "implications", "acute"], "article_id"=>1122212, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extracellular_HCV_Core_Protein_Induces_an_Immature_Regulatory_Phenotype_in_NK_Cells_Implications_for_Outcome_of_Acute_Infection_/1122212", "title"=>"Extracellular HCV-Core Protein Induces an Immature Regulatory Phenotype in NK Cells: Implications for Outcome of Acute Infection", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-30 03:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614811"], "description"=>"<p>Abbreviations: NKR = NK Receptor; M = Month; Ch = Chronic; Re = Resolved; † = p<0.05 versus normal control; * = p<0.05 Ch vs Re.</p>", "links"=>[], "tags"=>["immunology", "Gastroenterology and hepatology", "Infectious diseases", "Inflammatory diseases", "cells", "acute"], "article_id"=>1122209, "categories"=>["Biological Sciences"], "users"=>["Lucy Golden-Mason", "Young S. Hahn", "Michael Strong", "Linling Cheng", "Hugo R. Rosen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103219.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotype_of_natural_killer_NK_cells_in_acute_infection_over_time_/1122209", "title"=>"Phenotype of natural killer (NK) cells in acute infection over time.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-30 03:03:31"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2021", "month"=>"1"}

Relative Metric

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