{"id":2445,"date":"2013-08-14T00:00:00","date_gmt":"2013-08-14T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/potent-mechanism-helps-viruses-shut-down-bodys-defense-system-against-infection\/"},"modified":"2020-06-15T11:31:51","modified_gmt":"2020-06-15T18:31:51","slug":"potent-mechanism-helps-viruses-shut-down-bodys-defense-system-against-infection","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/potent-mechanism-helps-viruses-shut-down-bodys-defense-system-against-infection\/","title":{"rendered":"Potent mechanism helps viruses shut down body&#8217;s defense system against infection"},"content":{"rendered":"<p>LA JOLLA, CA\u2014Researchers at the Salk Institute for Biological Studies have discovered a powerful mechanism by which viruses such as influenza, West Nile and Dengue evade the body&#8217;s immune response and infect humans with these potentially deadly diseases. The findings may provide scientists with an attractive target for novel antiviral therapies.\n  <\/p>\n<p>\nPublished in the August 2013 issue of the journal <em><a href=\"http:\/\/www.cell.com\/cell-host-microbe\/abstract\/S1931-3128(13)00253-9\">Cell Host and Microbe<\/a><\/em>, the findings describe a novel mechanism that this group of so-called &#8220;enveloped viruses&#8221; uses to disarm the host&#8217;s innate immune response. The mechanism the scientists uncovered is based on these viruses activating a class of molecules, known as TAM receptors, which are located on the outside of certain immune cells.\n <\/p>\n<p>\nIn the immune system, TAM receptors are used by cells, such as macrophages and dendritic cells, to clean up dead cells, and they are also central inhibitors of the body&#8217;s innate immune response to bacteria, viruses and other pathogens.\n <\/p>\n<p>\nThe Salk scientists found that a substance called phosphatidylserine (PtdSer), which is found on the surface of enveloped viruses (viruses with an outer wrapping of a lipid membrane), binds to extracellular proteins and activates TAM receptors on immune cells. In dendritic cells, a type of immune cell that interacts with T and B cells to initiate the adaptive immune response, TAM receptor activation turns off a set of genes called interferons that play a key role in antiviral defense.\n <\/p>\n<div class=\"imageCaption530\"><img decoding=\"async\" alt=\"John Young, Erin Lew, Greg Lemke, Anna Zagorska, John Naughton\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2013\/01\/LemkeYoung-634.jpg\"\/><\/p>\n<p>\nFrom left: John Young, Erin Lew, Greg Lemke, Anna Zag\u00f3rska, John Naughton\n<\/p>\n<p>\u56fe\u7247\uff1a\u7531\u8428\u514b\u751f\u7269\u7814\u7a76\u6240\u63d0\u4f9b<\/p>\n<\/div>\n<p>\n&#8220;Our findings suggest a unique way in which TAM receptors contribute to the establishment of viral infection by disabling the interferon response,&#8221; says co-lead study author <a href=\"\/zh\/faculty\/young.html\/\">John A.T. Young<\/a>, \uff0c\u7d22\u5c14\u514b\u7814\u7a76\u6240\u7684\u6559\u6388 <a href=\"\/zh\/faculty\/immunology_microbial_pathogenesis_laboratory.html\/\">\u8bfa\u7c73\u65af\u57fa\u91d1\u4f1a\u514d\u75ab\u751f\u7269\u5b66\u4e0e\u5fae\u751f\u7269\u75c5\u539f\u5b66\u5b9e\u9a8c\u5ba4<\/a>. &#8220;As a consequence, the interferon-stimulated defense genes are not turned on, rendering the target cell more permissive for virus infection.&#8221;\n <\/p>\n<p>\nThis is a previously unknown mechanism for enveloped viruses, which are very common, to inhibit the body&#8217;s normal antiviral response. Since PtdSer exposure seems to be a general feature of enveloped viruses, the researchers say many different viruses may use the mechanism to counteract the cellular antiviral response in cells with TAM receptors.\n <\/p>\n<p>\nUnderstanding this mechanism allows researchers to work on developing broad-spectrum antiviral drugs that prevent viruses from shutting down the interferon response in cells by blocking TAM receptor activation. In their study, the Salk scientists tested a small-molecule drug called BMS-777607, initially developed for anti-cancer therapy, that does just that.\n <\/p>\n<p>\n &#8220;With this small molecule, viruses can&#8217;t activate TAM receptors, so they can&#8217;t shut down the interferon response,&#8221; says co-lead author <a href=\"\/zh\/faculty\/lemke.html\/\">Greg Lemke<\/a>, \uff0c\u7d22\u5c14\u514b\u7814\u7a76\u6240\u7684\u6559\u6388 <a href=\"\/zh\/faculty\/molecular_neurobiology_laboratory.html\/\">\u5206\u5b50\u795e\u7ecf\u751f\u7269\u5b66\u5b9e\u9a8c\u5ba4<\/a> and the Fran\u00e7oise Gilot-Salk Chair, in whose laboratory TAM receptors were discovered.\n <\/p>\n<p>\nWith other scientists around the country, the Salk researchers are testing a variety of small molecule drugs in series of different viruses, including West Nile, Dengue, influenza, Ebola, Marburg, and hepatitis B. These drugs work, in large part, by blocking the virus&#8217; ability to activate TAM receptors, thereby leaving the interferon-mediated antiviral response intact.\n <\/p>\n<p>\n&#8220;This is a completely novel approach,&#8221; says Young, who holds the Nomis Foundation Chair at Salk. &#8220;It is a way of exploiting a normal piece of the cellular machinery in the immune system to block virus infections.&#8221; And, if it works, it may prove to be an effective treatment to clear enveloped viruses during the acute phase of infection and perhaps also in chronic virus infections.\n <\/p>\n<p>\nOther researchers on the study were co-first authors Suchita Bhattacharyya and Anna Zag\u00f3rska, as well as Erin D. Lew and John Naughton, from the Salk Institute; Bimmi Shrestha and Michael S. Diamond of Washington University; and Carla V. Rothlin of Yale University.\n <\/p>\n<p>\n\u8fd9\u9879\u7814\u7a76\u5f97\u5230\u4e86...\u7684\u652f\u6301 <a href=\"http:\/\/www.nih.gov\/\">\u7f8e\u56fd\u56fd\u7acb\u536b\u751f\u7814\u7a76\u9662<\/a>, the Nomis and Auen Foundations, the James B. Pendleton Charitable Trust, a Salk Institute innovation grant, the <a href=\"http:\/\/www.hfsp.org\/\">Human Frontiers Science Program<\/a>, \uff0c\u548c <a href=\"http:\/\/www.lls.org\/\">\u767d\u8840\u75c5\u548c\u6dcb\u5df4\u7624\u534f\u4f1a<\/a>.\n<\/p>\n<p><strong><br \/>\n\u5173\u4e8e\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240\uff1a<\/strong><br \/>\n\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240\u662f\u4e16\u754c\u9876\u5c16\u7684\u57fa\u7840\u7814\u7a76\u673a\u6784\u4e4b\u4e00\uff0c\u5176\u56fd\u9645\u77e5\u540d\u7684\u6559\u804c\u4eba\u5458\u5728\u4e00\u4e2a\u72ec\u7279\u3001\u534f\u4f5c\u548c\u5bcc\u6709\u521b\u9020\u6027\u7684\u73af\u5883\u4e2d\uff0c\u6df1\u5165\u63a2\u7a76\u751f\u547d\u79d1\u5b66\u7684\u57fa\u672c\u95ee\u9898\u3002\u7d22\u5c14\u514b\u79d1\u5b66\u5bb6\u4eec\u81f4\u529b\u4e8e\u53d1\u73b0\u548c\u6307\u5bfc\u672a\u6765\u51e0\u4ee3\u7814\u7a76\u4eba\u5458\uff0c\u901a\u8fc7\u7814\u7a76\u795e\u7ecf\u79d1\u5b66\u3001\u9057\u4f20\u5b66\u3001\u7ec6\u80de\u548c\u690d\u7269\u751f\u7269\u5b66\u4ee5\u53ca\u76f8\u5173\u5b66\u79d1\uff0c\u5728\u764c\u75c7\u3001\u8870\u8001\u3001\u963f\u5c14\u8328\u6d77\u9ed8\u6c0f\u75c7\u3001\u7cd6\u5c3f\u75c5\u548c\u4f20\u67d3\u75c5\u7684\u8ba4\u8bc6\u65b9\u9762\u505a\u51fa\u4e86\u5f00\u521b\u6027\u7684\u8d21\u732e\u3002.\n<\/p>\n<p>\n\u5b66\u9662\u53d6\u5f97\u4e86\u8bb8\u591a\u6210\u5c31\uff0c\u83b7\u5f97\u4e86\u5305\u62ec\u8bfa\u8d1d\u5c14\u5956\u548c\u7f8e\u56fd\u56fd\u5bb6\u79d1\u5b66\u9662\u9662\u58eb\u5728\u5185\u7684\u65e0\u6570\u8363\u8a89\u3002\u8be5\u7814\u7a76\u6240\u7531\u810a\u9ad3\u7070\u8d28\u708e\u75ab\u82d7\u5148\u9a71 Jonas Salk \u535a\u58eb\u4e8e 1960 \u5e74\u521b\u7acb\uff0c\u662f\u4e00\u5bb6\u72ec\u7acb\u7684\u975e\u8425\u5229\u7ec4\u7ec7\u548c\u5efa\u7b51\u5730\u6807\u3002.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[96],"disease-research":[122,366],"class_list":["post-2445","disclosure","type-disclosure","status-publish","hentry","faculty-greg-lemke","disease-research-immune-system-biology","disease-research-infectious-disease"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Potent mechanism helps viruses shut down body&#039;s defense system against infection - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/potent-mechanism-helps-viruses-shut-down-bodys-defense-system-against-infection\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Potent mechanism helps viruses shut down body&#039;s defense system against infection - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA, CA\u2014Researchers at the Salk Institute for Biological Studies have discovered a powerful mechanism by which viruses such as influenza, West Nile and Dengue evade the body&#8217;s immune response and infect humans with these potentially deadly diseases. 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