Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state
To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial sex worker cohort in Nairobi and compared thei...
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creator | Songok, Elijah M Luo, Ma Liang, Ben Mclaren, Paul Kaefer, Nadine Apidi, Winnie Boucher, Genevieve Kimani, Joshua Wachihi, Charles Sekaly, Rafick Fowke, Keith Ball, Blake T Plummer, Francis A |
description | To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). Output data was analysed through ArrayAssist software (Agilent, San Jose CA). More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR |
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Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). Output data was analysed through ArrayAssist software (Agilent, San Jose CA). More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05). Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87%) had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0030048</identifier><identifier>PMID: 22291902</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; AIDS vaccines ; Antiviral agents ; Biology ; Biomarkers ; Blood ; Cell adhesion & migration ; Chemokines ; Cluster Analysis ; Clustering ; Cohort Studies ; Comparative analysis ; Cytokines ; Cytotoxicity ; Data processing ; DNA microarrays ; Down-Regulation - genetics ; Down-Regulation - immunology ; Female ; Gene expression ; Gene Expression Profiling ; Gene regulation ; Genes ; Genomes ; Gluconeogenesis ; Glycolysis ; Health aspects ; HIV ; HIV Infections - genetics ; HIV Infections - immunology ; HIV-1 - immunology ; Human immunodeficiency virus ; Humans ; Hybridization ; Immune response ; Immunity, Innate - genetics ; Infections ; Kenya ; Killer cells ; Ligands ; Lymphocyte Activation - genetics ; Lymphocyte Activation - immunology ; Lymphocytes T ; Medicine ; Microarray Analysis ; Natural killer cells ; Pathogenesis ; Pentose ; Pentose phosphate pathway ; Phosphates ; Prostitution ; Protein biosynthesis ; Protein synthesis ; Public health ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; Sex ; Sex industry ; Sex oriented businesses ; Sex Workers ; Sexually transmitted diseases ; Signal transduction ; Signaling ; STD ; T cell receptors ; T cells ; T-cell receptor ; Toxicity ; Type 2 diabetes ; Validation Studies as Topic ; Viruses ; Workers ; Working women</subject><ispartof>PloS one, 2012-01, Vol.7 (1), p.e30048-e30048</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Songok et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Songok et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-cf17eea2c36c5e7ea00bffa983cdfda73fad2602dbba4a0314177d5d6f9e357a3</citedby><cites>FETCH-LOGICAL-c691t-cf17eea2c36c5e7ea00bffa983cdfda73fad2602dbba4a0314177d5d6f9e357a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266890/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266890/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22291902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gray, Clive M.</contributor><creatorcontrib>Songok, Elijah M</creatorcontrib><creatorcontrib>Luo, Ma</creatorcontrib><creatorcontrib>Liang, Ben</creatorcontrib><creatorcontrib>Mclaren, Paul</creatorcontrib><creatorcontrib>Kaefer, Nadine</creatorcontrib><creatorcontrib>Apidi, Winnie</creatorcontrib><creatorcontrib>Boucher, Genevieve</creatorcontrib><creatorcontrib>Kimani, Joshua</creatorcontrib><creatorcontrib>Wachihi, Charles</creatorcontrib><creatorcontrib>Sekaly, Rafick</creatorcontrib><creatorcontrib>Fowke, Keith</creatorcontrib><creatorcontrib>Ball, Blake T</creatorcontrib><creatorcontrib>Plummer, Francis A</creatorcontrib><title>Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). Output data was analysed through ArrayAssist software (Agilent, San Jose CA). More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05). Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87%) had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>AIDS vaccines</subject><subject>Antiviral agents</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Cell adhesion & migration</subject><subject>Chemokines</subject><subject>Cluster Analysis</subject><subject>Clustering</subject><subject>Cohort Studies</subject><subject>Comparative analysis</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Data processing</subject><subject>DNA microarrays</subject><subject>Down-Regulation - genetics</subject><subject>Down-Regulation - immunology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genomes</subject><subject>Gluconeogenesis</subject><subject>Glycolysis</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV Infections - genetics</subject><subject>HIV Infections - immunology</subject><subject>HIV-1 - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Immune response</subject><subject>Immunity, Innate - genetics</subject><subject>Infections</subject><subject>Kenya</subject><subject>Killer cells</subject><subject>Ligands</subject><subject>Lymphocyte Activation - genetics</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Microarray Analysis</subject><subject>Natural killer cells</subject><subject>Pathogenesis</subject><subject>Pentose</subject><subject>Pentose phosphate pathway</subject><subject>Phosphates</subject><subject>Prostitution</subject><subject>Protein biosynthesis</subject><subject>Protein synthesis</subject><subject>Public health</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Sex</subject><subject>Sex industry</subject><subject>Sex oriented businesses</subject><subject>Sex Workers</subject><subject>Sexually transmitted diseases</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>STD</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>T-cell receptor</subject><subject>Toxicity</subject><subject>Type 2 diabetes</subject><subject>Validation Studies as Topic</subject><subject>Viruses</subject><subject>Workers</subject><subject>Working 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analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state</title><author>Songok, Elijah M ; Luo, Ma ; Liang, Ben ; Mclaren, Paul ; Kaefer, Nadine ; Apidi, Winnie ; Boucher, Genevieve ; Kimani, Joshua ; Wachihi, Charles ; Sekaly, Rafick ; Fowke, Keith ; Ball, Blake T ; Plummer, Francis A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-cf17eea2c36c5e7ea00bffa983cdfda73fad2602dbba4a0314177d5d6f9e357a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>AIDS vaccines</topic><topic>Antiviral agents</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>Cell adhesion & migration</topic><topic>Chemokines</topic><topic>Cluster Analysis</topic><topic>Clustering</topic><topic>Cohort 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One</addtitle><date>2012-01-26</date><risdate>2012</risdate><volume>7</volume><issue>1</issue><spage>e30048</spage><epage>e30048</epage><pages>e30048-e30048</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). Output data was analysed through ArrayAssist software (Agilent, San Jose CA). More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05). Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87%) had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22291902</pmid><doi>10.1371/journal.pone.0030048</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2012-01, Vol.7 (1), p.e30048-e30048 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1323433680 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Acquired immune deficiency syndrome AIDS AIDS vaccines Antiviral agents Biology Biomarkers Blood Cell adhesion & migration Chemokines Cluster Analysis Clustering Cohort Studies Comparative analysis Cytokines Cytotoxicity Data processing DNA microarrays Down-Regulation - genetics Down-Regulation - immunology Female Gene expression Gene Expression Profiling Gene regulation Genes Genomes Gluconeogenesis Glycolysis Health aspects HIV HIV Infections - genetics HIV Infections - immunology HIV-1 - immunology Human immunodeficiency virus Humans Hybridization Immune response Immunity, Innate - genetics Infections Kenya Killer cells Ligands Lymphocyte Activation - genetics Lymphocyte Activation - immunology Lymphocytes T Medicine Microarray Analysis Natural killer cells Pathogenesis Pentose Pentose phosphate pathway Phosphates Prostitution Protein biosynthesis Protein synthesis Public health Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA Sex Sex industry Sex oriented businesses Sex Workers Sexually transmitted diseases Signal transduction Signaling STD T cell receptors T cells T-cell receptor Toxicity Type 2 diabetes Validation Studies as Topic Viruses Workers Working women |
title | Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state |
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