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Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection
Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these pro...
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Published in: | PLoS neglected tropical diseases 2016-09, Vol.10 (9), p.e0004941-e0004941 |
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description | Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. |
doi_str_mv | 10.1371/journal.pntd.0004941 |
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Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0004941</identifier><identifier>PMID: 27632170</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aedes - chemistry ; Aedes - virology ; Animals ; Aquatic insects ; Biology and Life Sciences ; Colleges & universities ; Dengue - drug therapy ; Dengue fever ; Dengue virus ; Dengue Virus - drug effects ; Disease transmission ; Female ; Fractionation ; Genetic aspects ; Humans ; Immunoglobulins ; Immunology ; Infections ; Insect Proteins - pharmacology ; Liquid chromatography ; Lymph nodes ; Lymphatic system ; Medical research ; Medicine ; Medicine and Health Sciences ; Mice ; Mortality ; Mosquitoes ; Pathology ; Proteins ; Regulatory approval ; Risk factors ; Rodents ; Saliva - virology ; Salivary Glands - chemistry ; Salivary Proteins and Peptides - pharmacology ; Tropical diseases ; U937 Cells ; Vaccines ; Vector-borne diseases ; West Nile virus ; Yellow fever mosquito</subject><ispartof>PLoS neglected tropical diseases, 2016-09, Vol.10 (9), p.e0004941-e0004941</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: D7 Saliva Protein Inhibits Dengue Virus Infection. PLoS Negl Trop Dis 10(9): e0004941. doi:10.1371/journal.pntd.0004941</rights><rights>2016 Conway et al 2016 Conway et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: D7 Saliva Protein Inhibits Dengue Virus Infection. 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Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.</description><subject>Aedes - chemistry</subject><subject>Aedes - virology</subject><subject>Animals</subject><subject>Aquatic insects</subject><subject>Biology and Life Sciences</subject><subject>Colleges & universities</subject><subject>Dengue - drug therapy</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Dengue Virus - drug effects</subject><subject>Disease transmission</subject><subject>Female</subject><subject>Fractionation</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Infections</subject><subject>Insect Proteins - pharmacology</subject><subject>Liquid chromatography</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mortality</subject><subject>Mosquitoes</subject><subject>Pathology</subject><subject>Proteins</subject><subject>Regulatory approval</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Saliva - virology</subject><subject>Salivary Glands - chemistry</subject><subject>Salivary Proteins and Peptides - pharmacology</subject><subject>Tropical diseases</subject><subject>U937 Cells</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>West Nile virus</subject><subject>Yellow fever mosquito</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkltrFDEUxwdRbK1-A9EBQXzZNdfJ5EVZWi8LBQUvryGTnOymzCbbZKbQb2-2Oy27UvKQcPI7_3OtqtcYzTEV-ONVHFPQ_XwbBjtHCDHJ8JPqFEvKZ0RQ_vTgfVK9yPkKIS55i59XJ0Q0lGCBTqvPC7CQaw2r2-3g6wtR_9K9v9H1zxQH8KFehrXv_JDrCwirEeq_Po25WB2YwcfwsnrmdJ_h1XSfVX--fvl9_n12-ePb8nxxOTMNYcPM2c6B1AY7YZh2UthWk6bppNO4A0ycIchYwajlbUcYbaSjncROg5UEgNGz6u1ed9vHrKbas8ItkYxRLEQhlnvCRn2ltslvdLpVUXt1Z4hppXQavOlBcdEy1hjJmaSsM6QkhDjSrbC2pdQ1RevTFG3sNmANhCHp_kj0-Cf4tVrFG8UR4YjRIvBhEkjxeoQ8qI3PBvpeB4jjXd5lGAIJVNB3_6GPVzdRK10K8MHFEtfsRNWCiUZyLiUp1PwRqhwLG29iAOeL_cjh_YHDGnQ_rHPsx91o8zHI9qBJMecE7qEZGKndPt5nrXb7qKZ9LG5vDhv54HS_gPQfbqHbfw</recordid><startdate>20160915</startdate><enddate>20160915</enddate><creator>Conway, Michael J</creator><creator>Londono-Renteria, Berlin</creator><creator>Troupin, Andrea</creator><creator>Watson, Alan M</creator><creator>Klimstra, William B</creator><creator>Fikrig, Erol</creator><creator>Colpitts, Tonya M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160915</creationdate><title>Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection</title><author>Conway, Michael J ; Londono-Renteria, Berlin ; Troupin, Andrea ; Watson, Alan M ; Klimstra, William B ; Fikrig, Erol ; Colpitts, Tonya M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-fdbfe9ac1f7c4af97d8a266b9fa1be12fc20cd743d58b24369f3b91faed92ee43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aedes - chemistry</topic><topic>Aedes - virology</topic><topic>Animals</topic><topic>Aquatic insects</topic><topic>Biology and Life Sciences</topic><topic>Colleges & universities</topic><topic>Dengue - drug therapy</topic><topic>Dengue fever</topic><topic>Dengue virus</topic><topic>Dengue Virus - drug effects</topic><topic>Disease transmission</topic><topic>Female</topic><topic>Fractionation</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Infections</topic><topic>Insect Proteins - pharmacology</topic><topic>Liquid chromatography</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mortality</topic><topic>Mosquitoes</topic><topic>Pathology</topic><topic>Proteins</topic><topic>Regulatory approval</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Saliva - virology</topic><topic>Salivary Glands - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Conway, Michael J</au><au>Londono-Renteria, Berlin</au><au>Troupin, Andrea</au><au>Watson, Alan M</au><au>Klimstra, William B</au><au>Fikrig, Erol</au><au>Colpitts, Tonya M</au><au>Dinglasan, Rhoel Ramos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2016-09-15</date><risdate>2016</risdate><volume>10</volume><issue>9</issue><spage>e0004941</spage><epage>e0004941</epage><pages>e0004941-e0004941</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27632170</pmid><doi>10.1371/journal.pntd.0004941</doi><oa>free_for_read</oa></addata></record> |
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subjects | Aedes - chemistry Aedes - virology Animals Aquatic insects Biology and Life Sciences Colleges & universities Dengue - drug therapy Dengue fever Dengue virus Dengue Virus - drug effects Disease transmission Female Fractionation Genetic aspects Humans Immunoglobulins Immunology Infections Insect Proteins - pharmacology Liquid chromatography Lymph nodes Lymphatic system Medical research Medicine Medicine and Health Sciences Mice Mortality Mosquitoes Pathology Proteins Regulatory approval Risk factors Rodents Saliva - virology Salivary Glands - chemistry Salivary Proteins and Peptides - pharmacology Tropical diseases U937 Cells Vaccines Vector-borne diseases West Nile virus Yellow fever mosquito |
title | Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection |
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