{"id":18409,"date":"2017-01-11T12:00:00","date_gmt":"2017-01-11T17:00:00","guid":{"rendered":"https:\/\/dev.inrs.ca\/new-therapeutic-target-against-persistent-viral-infections\/"},"modified":"2020-11-16T14:19:12","modified_gmt":"2020-11-16T19:19:12","slug":"new-therapeutic-target-against-persistent-viral-infections","status":"publish","type":"post","link":"https:\/\/dev.inrs.ca\/en\/news\/new-therapeutic-target-against-persistent-viral-infections\/","title":{"rendered":"New therapeutic target against persistent viral infections"},"content":{"rendered":"<div class=\"single_entry_text\">\n<div><img decoding=\"async\" alt=\"\" src=\"\/sites\/default\/files\/actualites-images\/centre_iaf\/11-01-Alamarre-Lymphocyte.jpg\" style=\"width: 640px; height: 300px;\"\/><\/p>\n<hr\/>\n<\/div>\n<div><strong>Life is a question of balance, and the body is no exception. Expression levels of certain proteins can affect the immune system\u2019s ability to neutralize a virus. Type I interferons (IFN-I) are cytokines that were previously thought of as key contributors to the antiviral response, but emerging lines of evidence suggest that they may also participate in the establishment and maintenance of persistent viral infections. Professor <a href=\"http:\/\/www.dev.inrs.ca\/english\/alain-lamarre\" target=\"_blank\" rel=\"noopener noreferrer\">Alain Lamarre<\/a> and his team at the <a href=\"http:\/\/www.dev.inrs.ca\/english\/research-centres\/institut-armand-frappier-research-centre\" target=\"_blank\" rel=\"noopener noreferrer\">INRS-Institut Armand-Frappier Research Centre<\/a> have made significant advances in our understanding of the role of IFN-I in this setting. Their findings could lead to the development of novel therapeutic approaches against viral infections such as those caused by the hepatitis C virus (HCV) or the human immunodeficiency virus (HIV).\u00a0<\/strong><\/div>\n<div>\u00a0<\/div>\n<div>\u00a0<\/div>\n<div style=\"font-size:17px;\"><strong>Multiple type I interferon signalling pathways<\/strong><\/div>\n<div style=\"font-size:17px;\">\u00a0<\/div>\n<div>IFN-I is synthesized by a large number of cells and triggers diverse responses in target cells using various signalling pathways. During a typical virus infection, the virus replicates in the infected cell and induces IFN-I expression through pattern recognition receptors (PRRs) signalling. The cytokine then binds a specific receptor (IFNAR) to adjacent cells, which usually triggers reactions that stimulate the host\u2019s immune defences. However, the effect on chronic infections is different because prolonged exposure to IFN-I has negative immunomodulatory effects.<\/div>\n<div>\u00a0<\/div>\n<div>\u00a0<\/div>\n<div style=\"font-size:17px;\"><strong>The role of IFN-I in chronic viral infections<\/strong><\/div>\n<div>\u00a0<\/div>\n<div>Persistent viral infections, particularly those caused by HCV, HIV, and lymphocytic choriomeningitis virus (LCMV), an experimental model of persistent viral infections lead to a number of dysfunction to the humoral response such as an excessive production of non-specific antibodies (hypergammaglobulinemia) and a dysregulation of B cell subpopulations.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>The most recent work by professor Lamarre\u2019s team has focused on the molecular mechanisms that disrupt the immune system during chronic viral infections. The study\u2019s results highlight numerous mechanisms that explain the role of IFN-I in immune response disruptions. Using specific markers, professor Lamarre\u2019s team observed an abnormal increase in the expansion of TFH (a subpopulation of CD4+ T cells), which in this case triggers the expansion of non-specific B lymphocytes. The increased amount of TFH also reduces the proportion of other T cells that help fight infection.<\/div>\n<div>\u00a0<\/div>\n<div>The team has also demonstrated that IFN-I signalling affects the humoral response more directly. They have successfully restored antigen-specific responses by blocking B cell IFN-I receptors. Therefore, IFN-I acts directly on B cells to increase non-specific responses while impairing antigen-specific responses.<\/div>\n<div>\u00a0<\/div>\n<div>Professor Lamarre\u2019s team has identified the signalling pathways involved in disrupting the humoral immune response during the chronic phase of LCMV infection, but the complex responses caused by IFN-I require further characterization.\u00a0<span style=\"font-size: 12.16px;\">While it is unclear if sustained IFN-I production is a cause or consequence of persistent viral infection, it clearly plays an important role in humoral response disruption offering a promising therapeutic target against chronic viral infections.\u00a0<\/span><span style=\"color: rgb(79, 79, 79); font-family: Arial; font-size: 12px;\">\u2666<\/span><\/div>\n<div>\u00a0<\/div>\n<div>\u00a0<\/div>\n<div style=\"font-size:17px;\"><strong>Sources\u00a0<\/strong><\/div>\n<div>\u00a0<\/div>\n<div>Daugan, M. et <em>al<\/em>. (2016) <a href=\"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2016.00564\/full\" target=\"_blank\" rel=\"noopener noreferrer\">Type I Interferon Impairs Specific Antibody Responses Early during Establishment of LCMV Infection<\/a>.<em> Frontiers in Immunology<\/em><span style=\"font-size: 12.16px;\"><em>\u00a0<\/em>(Vol. 7 : 564).<\/span><\/div>\n<div>\u00a0<\/div>\n<div>Murira, A. and Lamarre, A. (2016)\u00a0<a href=\"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2016.00609\/full\" style=\"font-size: 12.16px;\" target=\"_blank\" rel=\"noopener noreferrer\">Type I Interferon Responses : From Friend to Foe in the Battle agains Chronic Viral Infection<\/a><span style=\"font-size: 12.16px;\">. <\/span><em style=\"font-size: 12.16px;\">Frontiers in Immunology<\/em><span style=\"font-size: 12.16px;\">\u00a0(Vol. 7 : 609).<\/span><\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Life is a question of balance, and the body is no exception. Expression levels of certain proteins can affect the immune system\u2019s ability to neutralize a virus. Type I interferons (IFN-I) are cytokines that were previously thought of as key contributors to the antiviral response, but emerging lines of evidence suggest that they may also [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":18410,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[688],"tags":[],"sectors":[732],"class_list":["post-18409","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innover-a-linrs-en","sectors-societe-en"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v24.6 (Yoast SEO v24.6) - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>New therapeutic target against persistent viral infections | INRS<\/title>\n<meta name=\"description\" content=\"Life is a question of balance, and the body is no exception. 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