Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes
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{"title"=>"Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes", "type"=>"journal", "authors"=>[{"first_name"=>"Samantha K.", "last_name"=>"Dunmire", "scopus_author_id"=>"55498294400"}, {"first_name"=>"Oludare A.", "last_name"=>"Odumade", "scopus_author_id"=>"8779358700"}, {"first_name"=>"Jean L.", "last_name"=>"Porter", "scopus_author_id"=>"56115299900"}, {"first_name"=>"Juan", "last_name"=>"Reyes-Genere", "scopus_author_id"=>"56114751300"}, {"first_name"=>"David O.", "last_name"=>"Schmeling", "scopus_author_id"=>"8919466400"}, {"first_name"=>"Hatice", "last_name"=>"Bilgic", "scopus_author_id"=>"23007702800"}, {"first_name"=>"Danhua", "last_name"=>"Fan", "scopus_author_id"=>"56115344800"}, {"first_name"=>"Emily C.", "last_name"=>"Baechler", "scopus_author_id"=>"6603079551"}, {"first_name"=>"Henry H.", "last_name"=>"Balfour", "scopus_author_id"=>"7103250933"}, {"first_name"=>"Kristin A.", "last_name"=>"Hogquist", "scopus_author_id"=>"7004012127"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84898623351", "sgr"=>"84898623351", "pui"=>"372833906", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24465555", "doi"=>"10.1371/journal.pone.0085422"}, "id"=>"3e105937-ecb9-3b24-9bde-380e0ea54d20", "abstract"=>"Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.", "link"=>"http://www.mendeley.com/research/primary-ebv-infection-induces-expression-profile-distinct-other-viruses-similar-hemophagocytic-syndr", "reader_count"=>36, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>4, "Other"=>4, "Student > Master"=>6, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>4, "Other"=>4, "Student > Master"=>6, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Materials Science"=>1, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>13, "Computer Science"=>4, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Computer Science"=>{"Computer Science"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Taiwan"=>1, "Mexico"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1349856"], "description"=>"<p>(A) Superarray analysis by qPCR was performed on 70 timepoints from 52 subjects to assess the time course of gene expression. Average fold changes for three groups of genes (Type I IRG, Type II IRG, and Cell Cycle as defined in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085422#pone.0085422.s001\" target=\"_blank\">Figure S1</a>) were determined for samples collected within the indicated time blocks. Fold changes are compared with healthy baselines. Error bars show the standard deviation. All three gene groupings had a p-value<0.05 when evaluated by ANOVA. (−20 days to −1 days N = 11; 0 days to 3 days N = 12; 4 days to 7 days N = 17; 8 days to 10 days N = 16). (B) The table shows the average fold change for nine select type I IRGs derived from microarray analysis for SLE, YFV, Flu, HRV, RSV, DENV, Poly IC, and EBV. (C) Heatmaps showing fold change as determined by qPCR for <i>OAS1</i>, <i>MX1</i>, and <i>HERC5</i> at multiple timepoints in EBV infection (top panel) or in other situations (bottom panel).</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "irgs", "enriched", "onset"], "article_id"=>902900, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g005", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Type_I_IRGs_are_slightly_enriched_before_onset_of_symptoms_but_some_IRGs_show_no_change_/902900", "title"=>"Type I IRGs are slightly enriched before onset of symptoms, but some IRGs show no change.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349853"], "description"=>"<p>Heatmap shows a list of the genes up/down regulated 3-fold during acute infection with EBV in comparison to subjects with other viral infections (YFV, Flu, HRV, RSV, and DENV), subjects injected with Poly IC, or patients with SLE. The color intensity represents fold changes in gene expression in comparison to either each subjects’ own healthy baseline (EBV, Flu, HRV, RSV, and Poly IC) or in comparison to healthy controls (SLE and DENV). Data is arranged as a hierarchical clustering of genes. The genes shown were derived from analysis of EBV subjects (fold change ≥3 and met a statistical significance cutoff of p-value of ≤0.05 with Bonferonni multiple-tests correction, please see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085422#pone.0085422.s006\" target=\"_blank\">Table S2</a> for fold change ≥2). Each column represents a single subject. Horizontal gray bars indicate that the gene of interest was not present in the analyzed dataset used for comparison. Vertical gray bars separate disease groupings. Colored boxes on the right represent specific clusters of genes discussed in the text: green box and green asterisks – EBV unique, purple box – genes in common between EBV and DENV, red – genes upregulated in all situations, blue – genes down-regulated in EBV and some other situations.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "epstein-barr", "causes", "patterns", "interferon", "driven"], "article_id"=>902897, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primary_Epstein_Barr_virus_infection_causes_distinct_expression_patterns_in_comparison_to_other_interferon_driven_responses_/902897", "title"=>"Primary Epstein-Barr virus infection causes distinct expression patterns in comparison to other interferon driven responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349851"], "description"=>"<p>Quantitative PCR analysis was performed on RNA prepared from sorted cells from peripheral blood of four subjects before and during acute EBV infection. (A) This panel shows the staining and sorting strategy for separation of CD8 T cells, B cells, NK cells, and monocytes. (B) Each subject’s respective cell type was compared with his or her own cell type at the preinfection time point. All acute samples were taken from subjects within a week of onset of symptoms. The average fold change of both type I and type II IRG as well as cell cycle genes for four subjects is shown. A paired t-test was used for statistical analysis. (C) Monocyte numbers were determined from complete blood counts of subjects at the acute and latent phases of EBV infection.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "cells", "monocytes", "upregulation", "groups", "acute"], "article_id"=>902895, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD8_T_cells_and_monocytes_show_upregulation_of_key_gene_groups_during_acute_infection_/902895", "title"=>"CD8+ T cells and monocytes show upregulation of key gene groups during acute infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349850"], "description"=>"<p>(A) Microarray analysis was performed on pre-infection, acute, and latent timepoints for the 10 subjects with primary EBV infection (listed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085422#pone.0085422.s005\" target=\"_blank\">Table S1</a>). 464 genes were shown to be significantly changed during the primary response to EBV at a fold change of ≥2 and a p-value ≤0.05. No genes were significantly changed during the latent phase of infection using the same criteria. (B) Ingenuity Pathway Analysis of the 464 acute genes revealed 14 pathways that were enriched amongst the genes that changed during primary EBV. These had a significant p-value (the negative log is shown) following evaluation with the Benjamini-Hochberg multiple tests correction. (C) A heatmap representation of the highest (≥3 fold) gene changes during the acute and latent stages of EBV infection.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "acute", "ebv", "latent"], "article_id"=>902894, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_distinct_gene_expression_profile_is_apparent_during_acute_EBV_infection_but_not_latent_infection_/902894", "title"=>"A distinct gene expression profile is apparent during acute EBV infection, but not latent infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349859"], "description"=>"<p>Data show the correlation between IRG gene expression and CD8 lymphocytosis in 42 subjects at timepoints within the first two weeks after symptom onset during primary EBV infection. The number of CD8 T cells per mL of peripheral blood was determined by flow cytometry (note: average at baseline was 0.25×10<sup>6</sup>). Superarray analysis by qPCR was performed to determine average fold changes for groups of Type I IRGs and Type II IRGs. Pearson correlation coefficients (r-values) and p-values are shown.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "ii", "irg", "correlates", "cd8", "lymphocytosis", "ebv"], "article_id"=>902903, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g007", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Type_II_IRG_gene_expression_correlates_with_CD8_lymphocytosis_in_primary_EBV_infection_/902903", "title"=>"Type II IRG gene expression correlates with CD8 lymphocytosis in primary EBV infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349860", "https://ndownloader.figshare.com/files/1349861", "https://ndownloader.figshare.com/files/1349862", "https://ndownloader.figshare.com/files/1349863", "https://ndownloader.figshare.com/files/1349864", "https://ndownloader.figshare.com/files/1349865", "https://ndownloader.figshare.com/files/1349866", "https://ndownloader.figshare.com/files/1349867"], "description"=>"<div><p>Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including <i>MX1, HERC5</i>, and <i>OAS1</i>, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.</p></div>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "ebv", "viruses", "hemophagocytic"], "article_id"=>902904, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085422.s001", "https://dx.doi.org/10.1371/journal.pone.0085422.s002", "https://dx.doi.org/10.1371/journal.pone.0085422.s003", "https://dx.doi.org/10.1371/journal.pone.0085422.s004", "https://dx.doi.org/10.1371/journal.pone.0085422.s005", "https://dx.doi.org/10.1371/journal.pone.0085422.s006", "https://dx.doi.org/10.1371/journal.pone.0085422.s007", "https://dx.doi.org/10.1371/journal.pone.0085422.s008"], "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primary_EBV_Infection_Induces_an_Expression_Profile_Distinct_from_Other_Viruses_but_Similar_to_Hemophagocytic_Syndromes_/902904", "title"=>"Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349858"], "description"=>"<p>The heatmap lists the genes that are up/down regulated ≥2 fold in SLE patients compared with subjects with viral infections or who were injected with Poly IC. The fold changes in gene expression are in comparison to healthy controls (SLE and DENV) or to each subjects’ own healthy baseline (EBV, YFV, Flu, HRV, and RSV). Pearson r-values indicating degree of similarity between SLE and each of the other conditons are shown at the bottom of the heatmap.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "influenza", "poly", "ic", "ebv"], "article_id"=>902902, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g006", "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SLE_has_high_similarity_to_influenza_and_Poly_IC_but_not_EBV_or_DENV_/902902", "title"=>"SLE has high similarity to influenza and Poly IC but not EBV or DENV.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349854"], "description"=>"<p>This heatmap compares the genes that change during primary EBV with DENV, and two syndromes: juvenile idiopathic arthritis with macrophage inflammatory syndrome (sJIA/MAS) and familial lymphocytic histiocytosis (FLH). The fold changes in gene expression are in comparison to either each subjects’ own healthy baseline (EBV) or healthy controls (DENV, sJIA/MAS and FLH). Genes shown had a fold change ≥3 in acute EBV and met a statistical significance cutoff of p-value of ≤0.05 with Bonferonni multiple-tests correction.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "immunology", "microbiology", "Virology", "systems biology", "Clinical immunology", "immunity", "Immune activation", "inflammation", "Infectious diseases", "Viral diseases", "Epstein-Barr virus infectious mononucleosis", "denv", "inflammatory"], "article_id"=>902898, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Samantha K. Dunmire", "Oludare A. Odumade", "Jean L. Porter", "Juan Reyes-Genere", "David O. Schmeling", "Hatice Bilgic", "Danhua Fan", "Emily C. Baechler", "Henry H. Balfour Jr", "Kristin A. Hogquist"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085422.g004", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EBV_has_high_similarity_to_DENV_and_inflammatory_syndromes_/902898", "title"=>"EBV has high similarity to DENV and inflammatory syndromes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:43:27"}

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