Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice
HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumo...
Gespeichert in:
Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2016-11, Vol.113 (46), p.13168-13173 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 13173 |
---|---|
container_issue | 46 |
container_start_page | 13168 |
container_title | Proceedings of the National Academy of Sciences - PNAS |
container_volume | 113 |
creator | Carroll, Virginia A. Lafferty, Mark K. Marchionni, Luigi Bryant, Joseph L. Gallo, Robert C. Garzino-Demo, Alfredo |
description | HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis. Approximately 15% of Tg26 mice spontaneously develop leukemia/lymphoma. We investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. The tumor cells resembled pro-B cells, and were CD19⁺IgM⁻IgD⁻CD93⁺CD43⁺CD21⁻CD23⁻VpreB⁺CXCR4⁺. Consistent with the pro-B-cell stage of B-cell development, microarray analysis revealed enrichment of transcripts, including Rag1, Rag2, CD93, Vpreb1, Vpreb3, and Igll1. We confirmed RAG1 expression in Tg26 tumors, and hypothesized that HIV-1 matrix protein p17 may directly induce RAG1 in B cells. Stimulation of human activated B cells with p17 enhanced RAG1 expression in three of seven donors, suggesting that intracellular signaling by p17 may lead to genomic instability and transformation. |
doi_str_mv | 10.1073/pnas.1615258113 |
format | Article |
fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5135339</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>26472490</jstor_id><sourcerecordid>26472490</sourcerecordid><originalsourceid>FETCH-LOGICAL-c476t-ca2dbd1125de999485ee0ff9506c807463ca71b43da20f8365275f42157594483</originalsourceid><addsrcrecordid>eNqNkr1vFDEQxa0IlBwhdapElmhoNhl_re0GCaJAIkWiAVrL5_XmfNq1F3sPcv89Pl1IgIpqivnNm3l-RuiUwAUByS6naMsFaYmgQhHCDtCCgCZNyzW8QAsAKhvFKT9Cr0pZA4AWCg7REZVS6zqzQN31w5R9KSFFnHp8c_utIXi0cw4PeMpp9iHiiUhsY4dtKckFO-_Yn2Fe4Q-N88OAh-04rdJocWX3AnO2sdz7GBweg_Ov0cveDsWfPNZj9PXj9Zerm-bu86fbq_d3jeOynRtnabfsCKGi81prroT30PdaQOsUSN4yZyVZctZZCr1iraBS9JwSIYXmXLFj9G6vO22Wo--cj_WQwUw5jDZvTbLB_N2JYWXu0w8jCBOM6Srw9lEgp-8bX2YzhrLzaKNPm2KIEiClYgr-A2W8mgDVVvTNP-g6bXKsL1EpzikTdXmlLveUy6mU7PunuwmYXdhmF7Z5DrtOnP9p94n_nW4FzvbAuswpP_dbLmn9IewXB0StbQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1844235533</pqid></control><display><type>article</type><title>Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice</title><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Carroll, Virginia A. ; Lafferty, Mark K. ; Marchionni, Luigi ; Bryant, Joseph L. ; Gallo, Robert C. ; Garzino-Demo, Alfredo</creator><creatorcontrib>Carroll, Virginia A. ; Lafferty, Mark K. ; Marchionni, Luigi ; Bryant, Joseph L. ; Gallo, Robert C. ; Garzino-Demo, Alfredo</creatorcontrib><description>HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis. Approximately 15% of Tg26 mice spontaneously develop leukemia/lymphoma. We investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. The tumor cells resembled pro-B cells, and were CD19⁺IgM⁻IgD⁻CD93⁺CD43⁺CD21⁻CD23⁻VpreB⁺CXCR4⁺. Consistent with the pro-B-cell stage of B-cell development, microarray analysis revealed enrichment of transcripts, including Rag1, Rag2, CD93, Vpreb1, Vpreb3, and Igll1. We confirmed RAG1 expression in Tg26 tumors, and hypothesized that HIV-1 matrix protein p17 may directly induce RAG1 in B cells. Stimulation of human activated B cells with p17 enhanced RAG1 expression in three of seven donors, suggesting that intracellular signaling by p17 may lead to genomic instability and transformation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1615258113</identifier><identifier>PMID: 27799525</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; HIV ; Human immunodeficiency virus ; Immunology ; Lentivirus ; Lymphoma ; Pathogenesis ; Protein expression ; Retroviridae ; RNA-protein interactions ; Rodents</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2016-11, Vol.113 (46), p.13168-13173</ispartof><rights>Volumes 1–89 and 106–113, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Nov 15, 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c476t-ca2dbd1125de999485ee0ff9506c807463ca71b43da20f8365275f42157594483</citedby><cites>FETCH-LOGICAL-c476t-ca2dbd1125de999485ee0ff9506c807463ca71b43da20f8365275f42157594483</cites><orcidid>0000-0002-4095-6950</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26472490$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26472490$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27799525$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carroll, Virginia A.</creatorcontrib><creatorcontrib>Lafferty, Mark K.</creatorcontrib><creatorcontrib>Marchionni, Luigi</creatorcontrib><creatorcontrib>Bryant, Joseph L.</creatorcontrib><creatorcontrib>Gallo, Robert C.</creatorcontrib><creatorcontrib>Garzino-Demo, Alfredo</creatorcontrib><title>Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis. Approximately 15% of Tg26 mice spontaneously develop leukemia/lymphoma. We investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. The tumor cells resembled pro-B cells, and were CD19⁺IgM⁻IgD⁻CD93⁺CD43⁺CD21⁻CD23⁻VpreB⁺CXCR4⁺. Consistent with the pro-B-cell stage of B-cell development, microarray analysis revealed enrichment of transcripts, including Rag1, Rag2, CD93, Vpreb1, Vpreb3, and Igll1. We confirmed RAG1 expression in Tg26 tumors, and hypothesized that HIV-1 matrix protein p17 may directly induce RAG1 in B cells. Stimulation of human activated B cells with p17 enhanced RAG1 expression in three of seven donors, suggesting that intracellular signaling by p17 may lead to genomic instability and transformation.</description><subject>Biological Sciences</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Immunology</subject><subject>Lentivirus</subject><subject>Lymphoma</subject><subject>Pathogenesis</subject><subject>Protein expression</subject><subject>Retroviridae</subject><subject>RNA-protein interactions</subject><subject>Rodents</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNkr1vFDEQxa0IlBwhdapElmhoNhl_re0GCaJAIkWiAVrL5_XmfNq1F3sPcv89Pl1IgIpqivnNm3l-RuiUwAUByS6naMsFaYmgQhHCDtCCgCZNyzW8QAsAKhvFKT9Cr0pZA4AWCg7REZVS6zqzQN31w5R9KSFFnHp8c_utIXi0cw4PeMpp9iHiiUhsY4dtKckFO-_Yn2Fe4Q-N88OAh-04rdJocWX3AnO2sdz7GBweg_Ov0cveDsWfPNZj9PXj9Zerm-bu86fbq_d3jeOynRtnabfsCKGi81prroT30PdaQOsUSN4yZyVZctZZCr1iraBS9JwSIYXmXLFj9G6vO22Wo--cj_WQwUw5jDZvTbLB_N2JYWXu0w8jCBOM6Srw9lEgp-8bX2YzhrLzaKNPm2KIEiClYgr-A2W8mgDVVvTNP-g6bXKsL1EpzikTdXmlLveUy6mU7PunuwmYXdhmF7Z5DrtOnP9p94n_nW4FzvbAuswpP_dbLmn9IewXB0StbQ</recordid><startdate>20161115</startdate><enddate>20161115</enddate><creator>Carroll, Virginia A.</creator><creator>Lafferty, Mark K.</creator><creator>Marchionni, Luigi</creator><creator>Bryant, Joseph L.</creator><creator>Gallo, Robert C.</creator><creator>Garzino-Demo, Alfredo</creator><general>National Academy of Sciences</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4095-6950</orcidid></search><sort><creationdate>20161115</creationdate><title>Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice</title><author>Carroll, Virginia A. ; Lafferty, Mark K. ; Marchionni, Luigi ; Bryant, Joseph L. ; Gallo, Robert C. ; Garzino-Demo, Alfredo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-ca2dbd1125de999485ee0ff9506c807463ca71b43da20f8365275f42157594483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biological Sciences</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Immunology</topic><topic>Lentivirus</topic><topic>Lymphoma</topic><topic>Pathogenesis</topic><topic>Protein expression</topic><topic>Retroviridae</topic><topic>RNA-protein interactions</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carroll, Virginia A.</creatorcontrib><creatorcontrib>Lafferty, Mark K.</creatorcontrib><creatorcontrib>Marchionni, Luigi</creatorcontrib><creatorcontrib>Bryant, Joseph L.</creatorcontrib><creatorcontrib>Gallo, Robert C.</creatorcontrib><creatorcontrib>Garzino-Demo, Alfredo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carroll, Virginia A.</au><au>Lafferty, Mark K.</au><au>Marchionni, Luigi</au><au>Bryant, Joseph L.</au><au>Gallo, Robert C.</au><au>Garzino-Demo, Alfredo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2016-11-15</date><risdate>2016</risdate><volume>113</volume><issue>46</issue><spage>13168</spage><epage>13173</epage><pages>13168-13173</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis. Approximately 15% of Tg26 mice spontaneously develop leukemia/lymphoma. We investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. The tumor cells resembled pro-B cells, and were CD19⁺IgM⁻IgD⁻CD93⁺CD43⁺CD21⁻CD23⁻VpreB⁺CXCR4⁺. Consistent with the pro-B-cell stage of B-cell development, microarray analysis revealed enrichment of transcripts, including Rag1, Rag2, CD93, Vpreb1, Vpreb3, and Igll1. We confirmed RAG1 expression in Tg26 tumors, and hypothesized that HIV-1 matrix protein p17 may directly induce RAG1 in B cells. Stimulation of human activated B cells with p17 enhanced RAG1 expression in three of seven donors, suggesting that intracellular signaling by p17 may lead to genomic instability and transformation.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>27799525</pmid><doi>10.1073/pnas.1615258113</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-4095-6950</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0027-8424 |
ispartof | Proceedings of the National Academy of Sciences - PNAS, 2016-11, Vol.113 (46), p.13168-13173 |
issn | 0027-8424 1091-6490 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5135339 |
source | JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
subjects | Biological Sciences HIV Human immunodeficiency virus Immunology Lentivirus Lymphoma Pathogenesis Protein expression Retroviridae RNA-protein interactions Rodents |
title | Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T05%3A11%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20of%20HIV-1%20matrix%20protein%20p17%20and%20association%20with%20B-cell%20lymphoma%20in%20HIV-1%20transgenic%20mice&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Carroll,%20Virginia%20A.&rft.date=2016-11-15&rft.volume=113&rft.issue=46&rft.spage=13168&rft.epage=13173&rft.pages=13168-13173&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1615258113&rft_dat=%3Cjstor_pubme%3E26472490%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1844235533&rft_id=info:pmid/27799525&rft_jstor_id=26472490&rfr_iscdi=true |