MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo
The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation i...
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| Veröffentlicht in: | Nature immunology 2002-06, Vol.3 (6), p.529-535 |
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| creator | Krmpotić, Astrid Busch, Dirk H. Bubić, Ivan Gebhardt, Friedemann Hengel, Hartmut Hasan, Milena Scalzo, Anthony A. Koszinowski, Ulrich H. Jonjić, Stipan |
| description | The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes
m06
and
m152
, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response. |
| doi_str_mv | 10.1038/ni799 |
| format | Article |
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m06
and
m152
, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni799</identifier><identifier>PMID: 12021778</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animals ; Animals, Congenic ; Biomedical and Life Sciences ; Biomedicine ; CD8-Positive T-Lymphocytes - immunology ; Cytomegalovirus - genetics ; Cytomegalovirus - immunology ; Cytomegalovirus - pathogenicity ; Cytotoxicity, Immunologic ; Female ; Gene Deletion ; Genes, Viral ; Histocompatibility Antigens Class I - metabolism ; Immune response ; Immunology ; Infectious Diseases ; Killer Cells, Natural - immunology ; Ligands ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; NK Cell Lectin-Like Receptor Subfamily K ; Receptors, Immunologic - metabolism ; Receptors, Natural Killer Cell ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - metabolism ; Viral Proteins - genetics ; Viral Proteins - immunology</subject><ispartof>Nature immunology, 2002-06, Vol.3 (6), p.529-535</ispartof><rights>Springer Nature America, Inc. 2002</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-a3345a1b36c906f3504a2437d738038008cc511a92f0d3bbdb7cdd54215c2bd63</citedby><cites>FETCH-LOGICAL-c404t-a3345a1b36c906f3504a2437d738038008cc511a92f0d3bbdb7cdd54215c2bd63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ni799$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ni799$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12021778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krmpotić, Astrid</creatorcontrib><creatorcontrib>Busch, Dirk H.</creatorcontrib><creatorcontrib>Bubić, Ivan</creatorcontrib><creatorcontrib>Gebhardt, Friedemann</creatorcontrib><creatorcontrib>Hengel, Hartmut</creatorcontrib><creatorcontrib>Hasan, Milena</creatorcontrib><creatorcontrib>Scalzo, Anthony A.</creatorcontrib><creatorcontrib>Koszinowski, Ulrich H.</creatorcontrib><creatorcontrib>Jonjić, Stipan</creatorcontrib><title>MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes
m06
and
m152
, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.</description><subject>Animals</subject><subject>Animals, Congenic</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cytomegalovirus - genetics</subject><subject>Cytomegalovirus - immunology</subject><subject>Cytomegalovirus - pathogenicity</subject><subject>Cytotoxicity, Immunologic</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Genes, Viral</subject><subject>Histocompatibility Antigens Class I - metabolism</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Killer Cells, Natural - immunology</subject><subject>Ligands</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Nude</subject><subject>NK Cell Lectin-Like Receptor Subfamily K</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Receptors, Natural Killer Cell</subject><subject>Viral Envelope Proteins - genetics</subject><subject>Viral Envelope Proteins - metabolism</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - immunology</subject><issn>1529-2908</issn><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkWtrHCEUhqU0NJfmLxQptBDKpsfLjM7HsL2FJC20234VR53BMKsbnVmaf1-3u2TZ4Ac9-ryH9_UgdE7gkgCTH4MXTfMCnZCKNjPakPrl0xnkMTrN-R6AcFHzV-iYUKBECHmCFnfzuz-4Hx5NXKU4Oh9wv-KATQydSxmvfZoyTi77POpgHB4jnn-SH_ACGzcMGetg8febXVHUa7-Or9FRp4fsznf7Gfr95fNi_m12--Pr9fzqdmY48HGmGeOVJi2rTQN1xyrgmnImrGCyRAKQxlSE6IZ2YFnb2lYYaytOSWVoa2t2ht5v-xbrD5PLo1r6vHGig4tTVoIIClLyAr59Bt7HKYXiTVFKBUjON9DlFur14JQPXRyTNmVZt_TlP1zny_0VkVJCXdVQBBcHgsKM7u_Y6ylndf3r5yH7bsuaFHNOrlOr5Jc6PSoCajNA9X-AhXuzczq1S2f31G5i-8y5PIXepX2Uw07_AKt5ndA</recordid><startdate>20020601</startdate><enddate>20020601</enddate><creator>Krmpotić, Astrid</creator><creator>Busch, Dirk H.</creator><creator>Bubić, Ivan</creator><creator>Gebhardt, Friedemann</creator><creator>Hengel, Hartmut</creator><creator>Hasan, Milena</creator><creator>Scalzo, Anthony A.</creator><creator>Koszinowski, Ulrich H.</creator><creator>Jonjić, Stipan</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020601</creationdate><title>MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo</title><author>Krmpotić, Astrid ; Busch, Dirk H. ; Bubić, Ivan ; Gebhardt, Friedemann ; Hengel, Hartmut ; Hasan, Milena ; Scalzo, Anthony A. ; Koszinowski, Ulrich H. ; Jonjić, Stipan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-a3345a1b36c906f3504a2437d738038008cc511a92f0d3bbdb7cdd54215c2bd63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Animals, Congenic</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cytomegalovirus - genetics</topic><topic>Cytomegalovirus - immunology</topic><topic>Cytomegalovirus - pathogenicity</topic><topic>Cytotoxicity, Immunologic</topic><topic>Female</topic><topic>Gene Deletion</topic><topic>Genes, Viral</topic><topic>Histocompatibility Antigens Class I - metabolism</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Infectious Diseases</topic><topic>Killer Cells, Natural - immunology</topic><topic>Ligands</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Nude</topic><topic>NK Cell Lectin-Like Receptor Subfamily K</topic><topic>Receptors, Immunologic - metabolism</topic><topic>Receptors, Natural Killer Cell</topic><topic>Viral Envelope Proteins - genetics</topic><topic>Viral Envelope Proteins - metabolism</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krmpotić, Astrid</creatorcontrib><creatorcontrib>Busch, Dirk H.</creatorcontrib><creatorcontrib>Bubić, Ivan</creatorcontrib><creatorcontrib>Gebhardt, Friedemann</creatorcontrib><creatorcontrib>Hengel, Hartmut</creatorcontrib><creatorcontrib>Hasan, Milena</creatorcontrib><creatorcontrib>Scalzo, Anthony A.</creatorcontrib><creatorcontrib>Koszinowski, Ulrich H.</creatorcontrib><creatorcontrib>Jonjić, Stipan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krmpotić, Astrid</au><au>Busch, Dirk H.</au><au>Bubić, Ivan</au><au>Gebhardt, Friedemann</au><au>Hengel, Hartmut</au><au>Hasan, Milena</au><au>Scalzo, Anthony A.</au><au>Koszinowski, Ulrich H.</au><au>Jonjić, Stipan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2002-06-01</date><risdate>2002</risdate><volume>3</volume><issue>6</issue><spage>529</spage><epage>535</epage><pages>529-535</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes
m06
and
m152
, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12021778</pmid><doi>10.1038/ni799</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Animals, Congenic Biomedical and Life Sciences Biomedicine CD8-Positive T-Lymphocytes - immunology Cytomegalovirus - genetics Cytomegalovirus - immunology Cytomegalovirus - pathogenicity Cytotoxicity, Immunologic Female Gene Deletion Genes, Viral Histocompatibility Antigens Class I - metabolism Immune response Immunology Infectious Diseases Killer Cells, Natural - immunology Ligands Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude NK Cell Lectin-Like Receptor Subfamily K Receptors, Immunologic - metabolism Receptors, Natural Killer Cell Viral Envelope Proteins - genetics Viral Envelope Proteins - metabolism Viral Proteins - genetics Viral Proteins - immunology |
| title | MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo |
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