{"id":1107,"date":"2016-10-06T14:45:17","date_gmt":"2016-10-06T14:45:17","guid":{"rendered":"http:\/\/www.virologyhighlights.com\/?p=1107"},"modified":"2018-05-25T08:31:47","modified_gmt":"2018-05-25T08:31:47","slug":"a-contrarian-view-of-how-the-immune-system-controls-virus-infections","status":"publish","type":"post","link":"https:\/\/www.elsevierblogs.com\/virology\/a-contrarian-view-of-how-the-immune-system-controls-virus-infections\/","title":{"rendered":"A contrarian view of how the immune system controls virus infections"},"content":{"rendered":"

Read the full article on ScienceDirect.<\/a><\/h3>\n

TCR independent suppression of CD8+<\/sup> T cell cytokine production mediated by IFN\u03b3 in vivo<\/em><\/h2>\n

Text by J. Lindsay Whitton<\/em><\/p>\n

Viruses survive and grow inside cells. The immune system has evolved to counter these infections using several strategies, two of which are (i) killing the infected cells (thus also killing the viruses that they contain) and (ii) showering nearby uninfected cells with specialized molecules (termed cytokines), which cause those cells to become more resistant to virus infection. One such cytokine, interferon gamma (IFN\u03b3), produced mainly by T cells and natural killer (NK) cells, is thought to play a key role, not only by limiting the spread of virus to uninfected cells but also by eradicating intracellular viruses without killing the cells. One might predict that such a powerful antiviral molecule would be abundantly and continually produced until the virus infection was under control. However, in our study, we found that IFN\u03b3 production by immune cells is extremely short-lived, terminating long before the virus infection has been completely cleared. Moreover, we showed that IFN\u03b3 can inhibit its own subsequent production, suggesting that IFN\u03b3 released from one immune cell may prevent neighboring immune cells from producing this cytokine.<\/p>\n

These unexpected observations have led us to entertain the notion that IFN\u03b3 might not be critically important for directly controlling many virus infections. This flew in the face of current dogma, so we were, initially, hesitant to pursue this hypothesis. However, its potential validity has been supported by work from other labs that demonstrated that human patients with genetic defects in the IFN\u03b3 signaling pathway can cope perfectly well with the vast majority of virus infections. So, at least in humans, IFN\u03b3 is not required for the control of viruses.<\/p>\n

\"whitton-highlight-diagram\"<\/p>\n

Figure legend<\/h3>\n

The possible means by which IFN\u03b3 acts during virus infection are shown in the diagram. Current understanding states that (arrow #1) IFN\u03b3 can act directly on virus-infected cells e.g., cells in the liver, heart, or pancreas (or most other tissues) to control the infection. However, as stated above, our data, and data from humans with genetic abnormalities, demonstrate that this direct effect \u2013 if it occurs \u2013 is not required for the ultimate clearance of virus. We currently favor the idea that any antiviral role of IFN\u03b3 is likely to be indirect, mediated by the cytokine acting on immune cells (#2), causing them to increase in number (#3); and these more abundant immune cells then clear the virus, perhaps in an IFN\u03b3-independent manner (#4).<\/p>\n

Introducing the authors<\/h3>\n

\"virology-image\"<\/p>\n

Martin Hosking (left) is a former postdoctoral colleague of Dr. J Lindsay Whitton (middle), whose lab studies viral pathogenesis, immunology, and vaccines. Claudia Flynn (right) is a Senior Research Associate in the lab.<\/p>\n

About the research<\/h3>\n

TCR independent suppression of CD8+ T cell cytokine production mediated by IFN\u03b3 in vivo<\/a><\/em><\/strong>
\nMartin P. Hosking, Claudia T. Flynn, J. Lindsay Whitton
\nVirology<\/em>, Volume 498, November 2016, Pages 69\u201381<\/p>\n","protected":false},"excerpt":{"rendered":"

Read the full article on ScienceDirect. TCR independent suppression of CD8+ T cell cytokine production mediated by IFN\u03b3 in vivo Text by J. Lindsay Whitton Viruses survive and grow inside cells. The immune system has evolved to counter these infections using several strategies, two of which are (i) killing the infected cells (thus also killing Read More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":1108,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5,632],"tags":[857,856,858],"class_list":["post-1107","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlighted-article","category-immunity-to-viruses","tag-cytokine","tag-ifn","tag-immune"],"_links":{"self":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/1107","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/comments?post=1107"}],"version-history":[{"count":7,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/1107\/revisions"}],"predecessor-version":[{"id":1116,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/1107\/revisions\/1116"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/media\/1108"}],"wp:attachment":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/media?parent=1107"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/categories?post=1107"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/tags?post=1107"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}