Also Included In: Tropical Diseases; Immune System / Vaccines
Article Date: 17 Aug 2013 - 0:00 PDT Current ratings for:
Body's defense system against infection shut down by potent mechanism in viruses
Researchers 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's immune response and infect humans with these potentially deadly diseases. The findings may provide scientists with an attractive target for novel antiviral therapies.
Published in the August issue of the journal Cell Host and Microbe, the findings describe a novel mechanism that this group of so-called "enveloped viruses" uses to disarm the host'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.
In 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's innate immune response to bacteria, viruses and other pathogens.
The 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.
"Our findings suggest a unique way in which TAM receptors contribute to the establishment of viral infection by disabling the interferon response," says co-lead study author John A.T. Young, a professor in Salk's Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis. "As a consequence, the interferon-stimulated defense genes are not turned on, rendering the target cell more permissive for virus infection."
This is a previously unknown mechanism for enveloped viruses, which are very common, to inhibit the body'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.
Understanding 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.
"With this small molecule, viruses can't activate TAM receptors, so they can't shut down the interferon response," says co-lead author Greg Lemke, a professor in Salk's Molecular Neurobiology Laboratory and the Françoise Gilot-Salk Chair, in whose laboratory TAM receptors were discovered.
With 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' ability to activate TAM receptors, thereby leaving the interferon-mediated antiviral response intact.
"This is a completely novel approach," says Young, who holds the Nomis Foundation Chair at Salk. "It is a way of exploiting a normal piece of the cellular machinery in the immune system to block virus infections." 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.
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.Visit our flu / cold / sars section for the latest news on this subject.
Other researchers on the study were co-first authors Suchita Bhattacharyya and Anna Zag?rska, 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.
The study was supported by the National Institutes of Health, the Nomis and Auen Foundations, the James B. Pendleton Charitable Trust, a Salk Institute innovation grant, the Human Frontiers Science Program, and the Leukemia and Lymphoma Society.
Enveloped Viruses Disable Innate Immune Responses in Dendritic Cells by Direct Activation of TAM Receptors
Cell Host & Microbe, Volume 14, Issue 2, 136-147, 14 August 2013; 10.1016/j.chom.2013.07.005
Salk Institute
Please use one of the following formats to cite this article in your essay, paper or report:MLA
17 Aug. 2013.
Please note: If no author information is provided, the source is cited instead.
'Body's defense system against infection shut down by potent mechanism in viruses'
Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.
If you write about specific medications or operations, please do not name health care professionals by name.
All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.
Contact Our News Editors
For any corrections of factual information, or to contact the editors please use our feedback form.
Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.
