Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters In Vivo Pro-inflammatory TNF-alpha Production during Acute Infection
Publication Date
August 30, 2012
Journal
PLOS Pathogens
Authors
Sara Rodríguez Martín, Kai Alexander Kropp, Vanessa Wilhelmi, Vanda Juranic Lisnic, et al
Volume
8
Issue
8
Pages
e1002901
DOI
http://doi.org/10.1371/journal.ppat.1002901
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1002901
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22952450
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431344
Europe PMC
http://europepmc.org/abstract/MED/22952450
Web of Science
000308558000067
Scopus
84866163013
Mendeley
http://www.mendeley.com/research/ablation-regulatory-ie1-protein-murine-cytomegalovirus-alters-vivo-proinflammatory-tnfalpha-producti
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Mendeley | Further Information

{"title"=>"Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters In Vivo Pro-inflammatory TNF-alpha Production during Acute Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Sara", "last_name"=>"Rodríguez-Martín", "scopus_author_id"=>"37112996800"}, {"first_name"=>"Kai Alexander", "last_name"=>"Kropp", "scopus_author_id"=>"35107440500"}, {"first_name"=>"Vanessa", "last_name"=>"Wilhelmi", "scopus_author_id"=>"25227832200"}, {"first_name"=>"Vanda Juranic", "last_name"=>"Lisnic", "scopus_author_id"=>"36453905200"}, {"first_name"=>"Wei Yuan", "last_name"=>"Hsieh", "scopus_author_id"=>"55167269900"}, {"first_name"=>"Mathieu", "last_name"=>"Blanc", "scopus_author_id"=>"37111910400"}, {"first_name"=>"Andrew", "last_name"=>"Livingston", "scopus_author_id"=>"8604507900"}, {"first_name"=>"Andreas", "last_name"=>"Busche", "scopus_author_id"=>"6508124131"}, {"first_name"=>"Hille", "last_name"=>"Tekotte", "scopus_author_id"=>"6603343782"}, {"first_name"=>"Martin", "last_name"=>"Messerle", "scopus_author_id"=>"7004636907"}, {"first_name"=>"Manfred", "last_name"=>"Auer", "scopus_author_id"=>"7006393995"}, {"first_name"=>"Iain", "last_name"=>"Fraser", "scopus_author_id"=>"7201478460"}, {"first_name"=>"Stipan", "last_name"=>"Jonjic", "scopus_author_id"=>"7004268029"}, {"first_name"=>"Ana", "last_name"=>"Angulo", "scopus_author_id"=>"7005419678"}, {"first_name"=>"Matthias J.", "last_name"=>"Reddehase", "scopus_author_id"=>"7005550691"}, {"first_name"=>"Peter", "last_name"=>"Ghazal", "scopus_author_id"=>"7005878579"}], "year"=>2012, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84866163013", "isbn"=>"1553-7374 (Electronic)\\n1553-7366 (Linking)", "issn"=>"15537366", "pmid"=>"22952450", "pui"=>"365631466", "doi"=>"10.1371/journal.ppat.1002901", "scopus"=>"2-s2.0-84866163013"}, "id"=>"5c70eba3-fcdb-35b1-9f8e-7cc209aa8573", "abstract"=>"Little is known about the role of viral genes in modulating host cytokine responses. Here we report a new functional role of the viral encoded IE1 protein of the murine cytomegalovirus in sculpting the inflammatory response in an acute infection. In time course experiments of infected primary macrophages (MΦs) measuring cytokine production levels, genetic ablation of the immediate-early 1 (ie1) gene results in a significant increase in TNFα production. Intracellular staining for cytokine production and viral early gene expression shows that TNFα production is highly associated with the productively infected MΦ population of cells. The ie1- dependent phenotype of enhanced MΦ TNFα production occurs at both protein and RNA levels. Noticeably, we show in a series of in vivo infection experiments that in multiple organs the presence of ie1 potently inhibits the pro-inflammatory cytokine response. From these experiments, levels of TNFα, and to a lesser extent IFNβ, but not the anti-inflammatory cytokine IL10, are moderated in the presence of ie1. The ie1- mediated inhibition of TNFα production has a similar quantitative phenotype profile in infection of susceptible (BALB/c) and resistant (C57BL/6) mouse strains as well as in a severe immuno-ablative model of infection. In vitro experiments with infected macrophages reveal that deletion of ie1 results in increased sensitivity of viral replication to TNFα inhibition. However, in vivo infection studies show that genetic ablation of TNFα or TNFRp55 receptor is not sufficient to rescue the restricted replication phenotype of the ie1 mutant virus. These results provide, for the first time, evidence for a role of IE1 as a regulator of the pro-inflammatory response and demonstrate a specific pathogen gene capable of moderating the host production of TNFα in vivo.", "link"=>"http://www.mendeley.com/research/ablation-regulatory-ie1-protein-murine-cytomegalovirus-alters-vivo-proinflammatory-tnfalpha-producti", "reader_count"=>13, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>2, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/584357"], "description"=>"<p>RAW264.7 macrophages were infected with MCMV or MCMVdie1 at an MOI of 1 for 24 h. Cells were fixed with 4% paraformaldehyde and double staining was performed for TNFα and MCMV E1 protein. DNA was counterstained with DAPI.</p>", "links"=>[], "tags"=>["situ", "staining", "viral-infected"], "article_id"=>254829, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_situ_staining_of_TNF_945_in_viral_infected_macrophages_/254829", "title"=>"In situ staining of TNFα in viral-infected macrophages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:20:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/584272"], "description"=>"<p>(A) Cells were mock-infected or infected with either MCMV or MCMVdie1 (MOI 1). IFNγ, IL10, IL12p70 and TNFα levels from cellular supernatants at 10 hpi were measured by flow cytometry-based CBA. (B) TNFα production after infection of RAW 264.7 macrophages. Cells were either mock-infected or infected with MCMV, MCMVdie1 or the MCMV IE1stop mutant (MOI 1). TNFα levels from the supernatants were determined by ELISA at 10 hpi. (C) TNFα production after infection of BMMΦ with MCMV, MCMVdie1 or MCMVdie3. Cytokine levels from cellular supernatants were measured by flow cytometry based CBA for 12 h time course, 16 and 24 hpi. (D) TNFα production from mock-infected BMMΦ or MCMV-, MCMVdie1- or MCMVrev-infected cells after 10 and 24 h. Cytokine levels were measured by ELISA. Experiments were done in triplicate and tested in duplicates. Bars show mean values with SE.</p>", "links"=>[], "tags"=>["infected"], "article_id"=>254747, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_production_in_infected_M_934_s_/254747", "title"=>"Cytokine production in infected MΦs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:19:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/584484"], "description"=>"<p>(A) NIH3T3 cells (−IE1) or Bam25 cells (+IE1) were transfected with 50 ng pTNF-gLuc expression plasmid or pcR3.1 as a negative control. For transfection control 50 ng of pGL3 were co-transfected in all cultures. 24 h post transfection cells were treated for 2 h with 300 nM TSA in PBS or a comparable dilution of DMSO (vehicle) and then LPS (100 ng/ml) stimulated. GLuc activity was measured and normalised to firefly activity per well. Bars show averages (n = 2) of a representative experiment (Error bars = SE). (B) RAW cells were transfected with 125 ng of IE1 expression plasmid pp89UC and 50 ng pGL3 for normalisation. 48 h after transfection cells were stimulated with LPS and normalised gLuc activity was determined. Bars show averages (n = 6) with SE.</p>", "links"=>[], "tags"=>["induced", "promoter"], "article_id"=>254953, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IE1_expression_can_moderate_induced_TNF_945_promoter_activity_/254953", "title"=>"IE1 expression can moderate induced TNFα promoter activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:22:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/585062"], "description"=>"<p>Groups of BALB/c mice (4 mice per group) were inoculated with either 3×10<sup>5</sup> or 3×10<sup>6</sup> PFU of parental MCMV or MCMVdie1, respectively. On day 4 and 7 post infection mice were killed and spleens, livers, kidneys and hearts (A, B, C and D, respectively) were harvested, weighted, and sonicated as a 10% (wt/vol) tissue homogenates in DMEM. <b>Left panels.</b> Viral titres were determined by standard plaque assay on MEFs. Grey lines show limit of detection. Black horizontal marks show median values. <b>Right panels.</b> Levels of TNFα in different organs of infected BALB/c mice. At indicated times organs were harvested, weighted and homogenated as a 10% (wt/v). TNFα levels were determined by ELISA from the homogenates. Mock infected mice were also included as a negative control. No significant differences were found in production of infectious virus between infections, except in kidneys at 4 dpi. Statistically significant differences in TNFα levels are shown as * = p<0.05 or ** = p<0.01.</p>", "links"=>[], "tags"=>["mcmv", "mcmvdie1", "levels", "organs", "infected"], "article_id"=>255527, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g009", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Growth_of_MCMV_and_MCMVdie1_and_TNF_945_levels_in_different_organs_of_infected_BALB_c_mice_/255527", "title"=>"Growth of MCMV and MCMVdie1 and TNFα levels in different organs of infected BALB/c mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:32:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/584849"], "description"=>"<p>Immune compromised female BALB/c mice (n = 3 per group) were infected with 1×10<sup>5</sup> PFU of MCMV or MCMVdie1 or not infected, i.e. uninfected but immune compromised mice to take into account that a 6.5 Gy total-body γ-irradiation by itself slightly stimulates the expression of the genes under investigation. The analysis was performed 10 days after infection. (A) Expression levels (ΔΔC<sub>T</sub> values) relative to β-actin transcripts. (B, C) Normalisation of the relative expression levels of TNFα, IFNβ, and IL10 to the numbers of E1 transcripts per 500 ng of total RNA (B) or to the numbers of infected MCP<sup>+</sup> cells per representative 10-mm<sup>2</sup> areas of liver tissue sections (C) in order to take account of differences in tissue infection density. Throughout, bars represent median values for three mice per experimental group. Variance bars indicate the range. P values for significance are indicated for group comparisons of interest (unpaired <i>t</i>-test, two-sided, performed with log-transformed data).</p>", "links"=>[], "tags"=>["situ", "activation", "cellular", "genes", "il10"], "article_id"=>255317, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g007", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_situ_activation_of_cellular_genes_TNF_945_IFN_946_and_IL10_during_infection_of_the_liver_/255317", "title"=>"In situ activation of cellular genes TNFα, IFNβ and IL10 during infection of the liver.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:28:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/584701"], "description"=>"<p>BMMΦs were mock infected or infected at an MOI of 1 with MCMV, MCMVdie1 or MCMVrev (n = 3). (A) Western blots for IκBα and the activated forms of the p38 and JNK kinases are shown. (B) Western Blots with transfected and infected RAW cells after LPS stimulation. RAW cells were transfected with IE1 expression plasmid pp89UC or a control vector (pEYFP-C2) and stimulated with 10 ng/ml LPS for 15 min or infected (MOI 1) and stimulated at 4 and 10 hpi, respectively.</p>", "links"=>[], "tags"=>["ie1-mediated", "p38", "jnk"], "article_id"=>255174, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Investigation_of_IE1_mediated_NF_954_B_p38_or_JNK_activation_/255174", "title"=>"Investigation of IE1-mediated NF-κB, p38 or JNK activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:26:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/585142"], "description"=>"<p>(A) BMMΦs were pre-treated for 24 h with TNFα as indicated and subsequently infected with either MCMV or MCMVdie1 (MOI 1). Total virus was measured by plaque assay at day 3 p.i. and dashed line indicates limit of detection with bars showing averages (n = 3) with SE. (B) Organs from infected C57B/6, TNFα<sup>−/−</sup> or TNFRp55<sup>−/−</sup> mice (2×10<sup>6</sup> PFU i.p.) were harvested at 4 d p.i. and homogenated for analysis with standard plaque assay (MCMV = grey circles; MCMVdie1 = open circles). Titres were normalised per sample weight, black lines indicate median values and dashed line represents limit of detection.</p>", "links"=>[], "tags"=>["blocks", "viral", "replication"], "article_id"=>255618, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g010", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TNF_blocks_viral_replication_in_vitro_but_is_not_essential_in_vivo_/255618", "title"=>"TNFα blocks viral replication <i>in vitro</i> but is not essential <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:33:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/307379", "https://ndownloader.figshare.com/files/307401", "https://ndownloader.figshare.com/files/307432", "https://ndownloader.figshare.com/files/307470", "https://ndownloader.figshare.com/files/307539", "https://ndownloader.figshare.com/files/307581", "https://ndownloader.figshare.com/files/307617", "https://ndownloader.figshare.com/files/307736"], "description"=>"<div><p>Little is known about the role of viral genes in modulating host cytokine responses. Here we report a new functional role of the viral encoded IE1 protein of the murine cytomegalovirus in sculpting the inflammatory response in an acute infection. In time course experiments of infected primary macrophages (MΦs) measuring cytokine production levels, genetic ablation of the immediate-early 1 (<em>ie1</em>) gene results in a significant increase in TNFα production. Intracellular staining for cytokine production and viral early gene expression shows that TNFα production is highly associated with the productively infected MΦ population of cells. The <em>ie1-</em> dependent phenotype of enhanced MΦ TNFα production occurs at both protein and RNA levels. Noticeably, we show in a series of <em>in vivo</em> infection experiments that in multiple organs the presence of <em>ie1</em> potently inhibits the pro-inflammatory cytokine response. From these experiments, levels of TNFα, and to a lesser extent IFNβ, but not the anti-inflammatory cytokine IL10, are moderated in the presence of <em>ie1</em>. The <em>ie1-</em> mediated inhibition of TNFα production has a similar quantitative phenotype profile in infection of susceptible (BALB/c) and resistant (C57BL/6) mouse strains as well as in a severe immuno-ablative model of infection. <em>In vitro</em> experiments with infected macrophages reveal that deletion of <em>ie1</em> results in increased sensitivity of viral replication to TNFα inhibition. However, <em>in vivo</em> infection studies show that genetic ablation of TNFα or TNFRp55 receptor is not sufficient to rescue the restricted replication phenotype of the <em>ie1</em> mutant virus. These results provide, for the first time, evidence for a role of IE1 as a regulator of the pro-inflammatory response and demonstrate a specific pathogen gene capable of moderating the host production of TNFα <em>in vivo</em>.</p> </div>", "links"=>[], "tags"=>["ablation", "ie1", "murine", "cytomegalovirus", "alters", "pro-inflammatory", "tnf-alpha", "acute"], "article_id"=>120637, "categories"=>["Cancer"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002901.s001", "https://dx.doi.org/10.1371/journal.ppat.1002901.s002", "https://dx.doi.org/10.1371/journal.ppat.1002901.s003", "https://dx.doi.org/10.1371/journal.ppat.1002901.s004", "https://dx.doi.org/10.1371/journal.ppat.1002901.s005", "https://dx.doi.org/10.1371/journal.ppat.1002901.s006", "https://dx.doi.org/10.1371/journal.ppat.1002901.s007", "https://dx.doi.org/10.1371/journal.ppat.1002901.s008"], "stats"=>{"downloads"=>0, "page_views"=>43, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Ablation_of_the_Regulatory_IE1_Protein_of_Murine_Cytomegalovirus_Alters_In_Vivo_Pro_inflammatory_TNF_alpha_Production_during_Acute_Infection/120637", "title"=>"Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters <em>In Vivo</em> Pro-inflammatory TNF-alpha Production during Acute Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-08-30 00:10:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/584204"], "description"=>"<p>(A) Genome copy number-to-PFU ratios of MCMV, MCMVdie1 and MCMVrev stocks. Viral DNA was extracted from 200 µl of viral stock from each strain and the number of genome copies per ml was measured by qPCR and related to infectivity measured as PFU by virus plaque assay. (B) Western blot shows equal infection of BMMΦ. Total protein was extracted at 24 hpi and Western blot was carried out to assess the expression of both IE1 and E1 viral proteins, showing that cells were equally infected. (C) (D) Growth of MCMV, MCMVdie1 and MCMVrev in NIH-3T3 and BMMΦ cells. Cells were infected with the different viruses at an MOI of 1. At indicated times cellular supernatant from infected NIH3T3 cells (C) and intracellular and extracellular virus from infected BMMΦ (D) were harvested and titrated by standard plaque assays in MEFs. Shown are the median values of 2 independent experiments (n = 3, each experiment) along with SD.</p>", "links"=>[], "tags"=>["mcmvdie1"], "article_id"=>254684, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_MCMV_MCMVdie1_and_MCMVrev_/254684", "title"=>"Comparison of MCMV, MCMVdie1 and MCMVrev.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:18:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/584954"], "description"=>"<p>BALB/c (A, B) or C57BL/6 mice (C, D) were infected with 3×10<sup>6</sup> PFU or 2×10<sup>6</sup> PFU, respectively, by the i.p. route. Groups of mice (4 to 5 mice per group) were inoculated with the specified dose of parental MCMV (light grey circles), MCMVdie1 (open circles) or MCMVrev (dark grey circles). On day 4 post infection mice were killed and the indicated organs were harvested, weighted, and sonicated as a 10% (wt/vol) tissue homogenate in DMEM. (A and C). Viral titres were determined by standard plaque assay on MEFs. Dashed lines show limit of detection. Dark horizontal marks show median values. (B and D). Ratios between TNFα levels and PFU in different organs at day 4 after infection are shown in a log scale. Statistically significant differences in viral titres and TNFα levels between MCMVrev or MCMV and MCMVdie1 are indicated by an asterisk (p<0.05).</p>", "links"=>[], "tags"=>["mcmvdie1", "mcmvrev", "organs", "infected"], "article_id"=>255416, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g008", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Growth_of_MCMV_MCMVdie1_and_MCMVrev_and_TNF_945_production_in_different_organs_from_infected_mice_/255416", "title"=>"Growth of MCMV, MCMVdie1 and MCMVrev and TNFα production in different organs from infected mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:30:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/584608"], "description"=>"<p>Total RNA was extracted at 10 h after mock infection or MCMV, MCMVdie1 and MCMVrev infection of BMMΦ. Quantitative RT-PCR was performed for relative expression levels of <i>tnf</i> mRNA in these cells. Shown are relative levels of <i>tnf</i> gene expression, which have been normalized against the <i>gapdh</i> gene expression and calibrated against MCMV induced-gene expression. SE bars are also shown (n = 3). Significance of differences in mRNA levels in MCMV and MCMVrev infected cells compared to mock infected cells was p<0.05 (*) and for comparison between MCMVdie1 and MCMV or mock p<0.01 (**), respectively (Student's <i>t</i>-test).</p>", "links"=>[], "tags"=>["Infectious diseases"], "article_id"=>255090, "categories"=>["Infectious Diseases"], "users"=>["Sara Rodríguez-Martín", "Kai Alexander Kropp", "Vanessa Wilhelmi", "Vanda Juranic Lisnic", "Wei Yuan Hsieh", "Mathieu Blanc", "Andrew Livingston", "Andreas Busche", "Hille Tekotte", "Martin Messerle", "Manfred Auer", "Iain Fraser", "Stipan Jonjic", "Ana Angulo", "Matthias J. Reddehase", "Peter Ghazal"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002901.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_tnf_gene_expression_in_infected_BMM_/255090", "title"=>"<i>tnf</i> gene expression in infected-BMMΦ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-30 01:24:50"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"31", "full-text"=>"36", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
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Relative Metric

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