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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2019-10-01T00:00:00-04:00" class="date-display-single">October 1, 2019</span></p><div class='syndicate'><h1>Disrupting host protein blocks enterovirus infections in mice</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Researchers found that enteroviruses, which cause many cases of the common cold as well as more serious diseases, need a host protein called SETD3.</li>
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<li>The findings suggest a strategy to explore for treating enterovirus infections without harming normal cells.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Enterovirus EV-D68 virions">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2019/20190927-virus-brown.jpg?itok=eSVJuvBC&timestamp=1569871817 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2019/20190927-virus-brown.jpg?itok=AT7qIVLM&timestamp=1569871817 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2019/20190927-virus-brown.jpg?itok=-r0bb6pY&timestamp=1569871817 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2019/20190927-virus-brown.jpg?itok=oVT4gAff&timestamp=1569871817 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2019/20190927-virus-brown.jpg?itok=U9jczJFC&timestamp=1569871817 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2019/20190927-virus-brown.jpg?itok=AT7qIVLM&timestamp=1569871817" alt="Electron microscope image of EV-D68 virions" title="Enterovirus EV-D68 virions" />
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</picture><span class="caption">The enterovirus EV-D68, which has been linked to acute flaccid myelitis, was one of the enteroviruses used in the study. </span><span class="credit">Cynthia S. Goldsmith and Yiting Zhang, CDC</span></div>
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</div><p>Enteroviruses cause millions of infections each year in the United States. Most of the resulting diseases, like the common cold, are mild. But some enteroviruses can cause serious or even deadly conditions. Recently, an enterovirus was linked with cases of acute flaccid myelitis, a mysterious condition that causes paralysis.</p>
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<p>There are over a hundred types of enteroviruses. That makes development of a vaccine or virus-specific treatments challenging. Researchers have been studying how the viruses interact with their hosts. Targeting proteins in the human body that the viruses depend on may be an effective way to treat enterovirus infections.</p>
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<p>A team led by Dr. Jan Carette from Stanford University has been working to identify human proteins that are essential for viral infection. In their new study, they examined whether breaking the link between an enterovirus protein and an essential host protein could stop infection in human cells and in mice.</p>
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<p>The research was funded in part by NIH’s National Institute of General Medical Sciences (NIGMS) and National Institute of Allergy and Infectious Diseases (NIAID). Results were published on September 16, 2019, in <em>Nature Microbiology</em>.</p>
|
||
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||
<p>The researchers first did a genome-wide genetic screen. They used a gene-editing technology called CRISPR-Cas9 to disrupt single genes at a time in laboratory cells. They then infected the modified cells with one of two enteroviruses.</p>
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||
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||
<p>Three genes were critical for both viruses to replicate (make copies) inside the cells. Two of the genes were previously described. The third, <em>SETD3,</em> codes for a protein that helps regulate the cell’s internal structures.</p>
|
||
|
||
<p>The scientists found that other families of viruses didn’t need this protein to replicate. However, all of the enteroviruses tested did. Additional research showed that enteroviruses could get into cells that lacked SETD3 but weren’t able to reproduce and spread.</p>
|
||
|
||
<p>Further work showed that SETD3 interacts with a viral protein called 2A. This affinity between the two proteins was seen in all tested enteroviruses. When the researchers prevented 2A from binding to SETD3, the virus wasn’t able to replicate.</p>
|
||
|
||
<p>The scientists then investigated the effects of removing SETD3 from human cells and mice. Human lung cells engineered to lack SETD3 had a 100-fold reduction in viral replication after infection compared to normal lung cells. Mice engineered to lack SETD3, which were able to grow and develop, showed no symptoms of infection after injection of deadly enteroviruses.</p>
|
||
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<p>Additional experiments showed that enteroviruses don’t rely on the activity of the SETD3 protein that’s required for its normal function in the human body.</p>
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<p>“This gives us hope that we can develop a drug with broad antiviral activity against not only the common cold but maybe all enteroviruses, without even disturbing SETD3’s regular function in our cells,” Carette says.</p>
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||
<p>Such an approach to drug development would aim to disrupt the interaction between SETD3 and 2A instead of shutting down SETD3 itself.</p>
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<p>—by Sharon Reynolds</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/enterovirus-infection-linked-acute-flaccid-myelitis" target="_top">Enterovirus Infection Linked to Acute Flaccid Myelitis</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/genetic-alteration-child-reveals-immune-response-pathway-common-cold" target="_top">Genetic Alteration in Child Reveals Immune Response Pathway in Common Cold</a></li><li><a href="https://newsinhealth.nih.gov/2014/10/cold-flu-or-allergy" target="_top">Cold, Flu, or Allergy?</a></li><li><a href="https://newsinhealth.nih.gov/2012/06/catching-cold-when-its-warm" target="_top">Catching a Cold When It’s Warm</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/31527793">Enterovirus pathogenesis requires the host methyltransferase SETD3.</a> Diep J, Ooi YS, Wilkinson AW, Peters CE, Foy E, Johnson JR, Zengel J, Ding S, Weng KF, Laufman O, Jang G, Xu J, Young T, Verschueren E, Kobluk KJ, Elias JE, Sarnow P, Greenberg HB, Hüttenhain R, Nagamine CM, Andino R, Krogan NJ, Gozani O, Carette JE. <em>Nat Microbiol</em>. 2019 Sep 16. doi: 10.1038/s41564-019-0551-1. [Epub ahead of print] PMID: 31527793.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of General Medical Sciences (NIGMS) and National Institute of Allergy and Infectious Diseases (NIAID); National Science Foundation; Stanford University; American Asthma Foundation; David and Lucile Packard Foundation; U.S. Department of Veterans Affairs; Thrasher Research Fund.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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