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Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response
Abstract We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural contr...
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Published in: | The Journal of infectious diseases 2021-11, Vol.224 (9), p.1593-1598 |
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container_issue | 9 |
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container_title | The Journal of infectious diseases |
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creator | Wu, Guoxin Zuck, Paul Goh, Shih Lin Milush, Jeffrey M Vohra, Poonam Wong, Joseph K Somsouk, Ma Yukl, Steven A Shacklett, Barbara L Chomont, Nicolas Haase, Ashley T Hatano, Hiroyu Schacker, Timothy W Deeks, Steven G Hazuda, Daria J Hunt, Peter W Howell, Bonnie J |
description | Abstract
We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural controllers. During ART, gut p24 expression is more strongly associated both with HIV-specific CD8+ T-cell frequency and plasma soluble CD14 levels than gut HIV RNA expression. This study supports using gag p24 as a marker of HIV expression in HIV+ tissues to study effects of viral persistence and to monitor efficacy of treatment in HIV-based clearance studies.
Continuous expression of HIV protein in lymphoid tissues despite prolonged viral suppression helps explain persistent immune activation and HIV-specific T-cell responses. Measuring HIV protein in tissues will likely be important for understanding mechanisms of persistence and evaluating future cure approaches. |
doi_str_mv | 10.1093/infdis/jiab121 |
format | article |
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We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural controllers. During ART, gut p24 expression is more strongly associated both with HIV-specific CD8+ T-cell frequency and plasma soluble CD14 levels than gut HIV RNA expression. This study supports using gag p24 as a marker of HIV expression in HIV+ tissues to study effects of viral persistence and to monitor efficacy of treatment in HIV-based clearance studies.
Continuous expression of HIV protein in lymphoid tissues despite prolonged viral suppression helps explain persistent immune activation and HIV-specific T-cell responses. Measuring HIV protein in tissues will likely be important for understanding mechanisms of persistence and evaluating future cure approaches.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiab121</identifier><identifier>PMID: 33693750</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Antiretroviral drugs ; Antiretroviral therapy ; Biomarkers - blood ; Biopsy ; CD14 antigen ; CD4 antigen ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - immunology ; CD8 antigen ; Female ; gag Gene Products, Human Immunodeficiency Virus - metabolism ; Gag protein ; HIV ; HIV Core Protein p24 - genetics ; HIV Core Protein p24 - immunology ; HIV Infections - drug therapy ; HIV Infections - genetics ; HIV Infections - immunology ; HIV-1 - immunology ; Human immunodeficiency virus ; Humans ; Immune clearance ; Immune system ; Lymph nodes ; Lymphocyte Activation ; Lymphocytes T ; Major and Brief Reports ; p24 Protein</subject><ispartof>The Journal of infectious diseases, 2021-11, Vol.224 (9), p.1593-1598</ispartof><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-f2afd2a053585887780755fb4596cb9ce7c2777f135f9db042f671ff5c62e8483</citedby><cites>FETCH-LOGICAL-c452t-f2afd2a053585887780755fb4596cb9ce7c2777f135f9db042f671ff5c62e8483</cites><orcidid>0000-0001-6116-3645 ; 0000-0002-5915-9943</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33693750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Guoxin</creatorcontrib><creatorcontrib>Zuck, Paul</creatorcontrib><creatorcontrib>Goh, Shih Lin</creatorcontrib><creatorcontrib>Milush, Jeffrey M</creatorcontrib><creatorcontrib>Vohra, Poonam</creatorcontrib><creatorcontrib>Wong, Joseph K</creatorcontrib><creatorcontrib>Somsouk, Ma</creatorcontrib><creatorcontrib>Yukl, Steven A</creatorcontrib><creatorcontrib>Shacklett, Barbara L</creatorcontrib><creatorcontrib>Chomont, Nicolas</creatorcontrib><creatorcontrib>Haase, Ashley T</creatorcontrib><creatorcontrib>Hatano, Hiroyu</creatorcontrib><creatorcontrib>Schacker, Timothy W</creatorcontrib><creatorcontrib>Deeks, Steven G</creatorcontrib><creatorcontrib>Hazuda, Daria J</creatorcontrib><creatorcontrib>Hunt, Peter W</creatorcontrib><creatorcontrib>Howell, Bonnie J</creatorcontrib><title>Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural controllers. During ART, gut p24 expression is more strongly associated both with HIV-specific CD8+ T-cell frequency and plasma soluble CD14 levels than gut HIV RNA expression. This study supports using gag p24 as a marker of HIV expression in HIV+ tissues to study effects of viral persistence and to monitor efficacy of treatment in HIV-based clearance studies.
Continuous expression of HIV protein in lymphoid tissues despite prolonged viral suppression helps explain persistent immune activation and HIV-specific T-cell responses. Measuring HIV protein in tissues will likely be important for understanding mechanisms of persistence and evaluating future cure approaches.</description><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Biomarkers - blood</subject><subject>Biopsy</subject><subject>CD14 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8 antigen</subject><subject>Female</subject><subject>gag Gene Products, Human Immunodeficiency Virus - metabolism</subject><subject>Gag protein</subject><subject>HIV</subject><subject>HIV Core Protein p24 - genetics</subject><subject>HIV Core Protein p24 - immunology</subject><subject>HIV Infections - drug therapy</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>Immune clearance</subject><subject>Immune system</subject><subject>Lymph nodes</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes T</subject><subject>Major and Brief Reports</subject><subject>p24 Protein</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkU1rFTEUhoMo9lrdupSAG11Mm4_J10aQS20vVASpugyZTNLmOpOMyYzYf9-UuRZ14yoc8pyH8_IC8BKjE4wUPQ3R96Gc7oPpMMGPwAYzKhrOMX0MNggR0mCp1BF4VsoeIdRSLp6CI0q5ooKhDRjPzTWcSAt3BRr40eTvLsPk4cUymgh347jE1DsfbHDR3sKvIS8Fnv2asislpAhDhFehlMXV9djDbcrZDWau47cw36wCBz-7MqVY3HPwxJuhuBeH9xh8-XB2tb1oLj-d77bvLxvbMjI3nhjfE4MYZZJJKYREgjHftUxx2ynrhCVCCI8p86rvUEs8F9h7ZjlxspX0GLxbvdPSja63Ls7ZDHrKYTT5VicT9N8_Mdzo6_RTS6aUxKgK3hwEOf2o4WY9hmLdMJjo0lI0YQhRQRETFX39D7pPS441niYcC8UFV22lTlbK5lRKdv7hGIz0fZN6bVIfmqwLr_6M8ID_rq4Cb1cgLdP_ZHcGQqqP</recordid><startdate>20211116</startdate><enddate>20211116</enddate><creator>Wu, Guoxin</creator><creator>Zuck, Paul</creator><creator>Goh, Shih Lin</creator><creator>Milush, Jeffrey M</creator><creator>Vohra, Poonam</creator><creator>Wong, Joseph K</creator><creator>Somsouk, Ma</creator><creator>Yukl, Steven A</creator><creator>Shacklett, Barbara L</creator><creator>Chomont, Nicolas</creator><creator>Haase, Ashley T</creator><creator>Hatano, Hiroyu</creator><creator>Schacker, Timothy W</creator><creator>Deeks, Steven G</creator><creator>Hazuda, Daria J</creator><creator>Hunt, Peter W</creator><creator>Howell, Bonnie J</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6116-3645</orcidid><orcidid>https://orcid.org/0000-0002-5915-9943</orcidid></search><sort><creationdate>20211116</creationdate><title>Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response</title><author>Wu, Guoxin ; Zuck, Paul ; Goh, Shih Lin ; Milush, Jeffrey M ; Vohra, Poonam ; Wong, Joseph K ; Somsouk, Ma ; Yukl, Steven A ; Shacklett, Barbara L ; Chomont, Nicolas ; Haase, Ashley T ; Hatano, Hiroyu ; Schacker, Timothy W ; Deeks, Steven G ; Hazuda, Daria J ; Hunt, Peter W ; Howell, Bonnie J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-f2afd2a053585887780755fb4596cb9ce7c2777f135f9db042f671ff5c62e8483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Biomarkers - blood</topic><topic>Biopsy</topic><topic>CD14 antigen</topic><topic>CD4 antigen</topic><topic>CD4 Lymphocyte Count</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8 antigen</topic><topic>Female</topic><topic>gag Gene Products, Human Immunodeficiency Virus - metabolism</topic><topic>Gag protein</topic><topic>HIV</topic><topic>HIV Core Protein p24 - genetics</topic><topic>HIV Core Protein p24 - immunology</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - genetics</topic><topic>HIV Infections - immunology</topic><topic>HIV-1 - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immune clearance</topic><topic>Immune system</topic><topic>Lymph nodes</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes T</topic><topic>Major and Brief Reports</topic><topic>p24 Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Guoxin</creatorcontrib><creatorcontrib>Zuck, Paul</creatorcontrib><creatorcontrib>Goh, Shih Lin</creatorcontrib><creatorcontrib>Milush, Jeffrey M</creatorcontrib><creatorcontrib>Vohra, Poonam</creatorcontrib><creatorcontrib>Wong, Joseph K</creatorcontrib><creatorcontrib>Somsouk, Ma</creatorcontrib><creatorcontrib>Yukl, Steven A</creatorcontrib><creatorcontrib>Shacklett, Barbara L</creatorcontrib><creatorcontrib>Chomont, Nicolas</creatorcontrib><creatorcontrib>Haase, Ashley T</creatorcontrib><creatorcontrib>Hatano, Hiroyu</creatorcontrib><creatorcontrib>Schacker, Timothy W</creatorcontrib><creatorcontrib>Deeks, Steven G</creatorcontrib><creatorcontrib>Hazuda, Daria J</creatorcontrib><creatorcontrib>Hunt, Peter W</creatorcontrib><creatorcontrib>Howell, Bonnie J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Guoxin</au><au>Zuck, Paul</au><au>Goh, Shih Lin</au><au>Milush, Jeffrey M</au><au>Vohra, Poonam</au><au>Wong, Joseph K</au><au>Somsouk, Ma</au><au>Yukl, Steven A</au><au>Shacklett, Barbara L</au><au>Chomont, Nicolas</au><au>Haase, Ashley T</au><au>Hatano, Hiroyu</au><au>Schacker, Timothy W</au><au>Deeks, Steven G</au><au>Hazuda, Daria J</au><au>Hunt, Peter W</au><au>Howell, Bonnie J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2021-11-16</date><risdate>2021</risdate><volume>224</volume><issue>9</issue><spage>1593</spage><epage>1598</epage><pages>1593-1598</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>Abstract
We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural controllers. During ART, gut p24 expression is more strongly associated both with HIV-specific CD8+ T-cell frequency and plasma soluble CD14 levels than gut HIV RNA expression. This study supports using gag p24 as a marker of HIV expression in HIV+ tissues to study effects of viral persistence and to monitor efficacy of treatment in HIV-based clearance studies.
Continuous expression of HIV protein in lymphoid tissues despite prolonged viral suppression helps explain persistent immune activation and HIV-specific T-cell responses. Measuring HIV protein in tissues will likely be important for understanding mechanisms of persistence and evaluating future cure approaches.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33693750</pmid><doi>10.1093/infdis/jiab121</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0001-6116-3645</orcidid><orcidid>https://orcid.org/0000-0002-5915-9943</orcidid><oa>free_for_read</oa></addata></record> |
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source | Oxford Journals Online |
subjects | Antiretroviral drugs Antiretroviral therapy Biomarkers - blood Biopsy CD14 antigen CD4 antigen CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology CD8 antigen Female gag Gene Products, Human Immunodeficiency Virus - metabolism Gag protein HIV HIV Core Protein p24 - genetics HIV Core Protein p24 - immunology HIV Infections - drug therapy HIV Infections - genetics HIV Infections - immunology HIV-1 - immunology Human immunodeficiency virus Humans Immune clearance Immune system Lymph nodes Lymphocyte Activation Lymphocytes T Major and Brief Reports p24 Protein |
title | Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response |
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