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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="2022-11-08T00:00:00-05:00" class="date-display-single">November 8, 2022</span></p><div class='syndicate'><h1>Structure of hepatitis C proteins reveals viral vulnerabilities </h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Researchers determined the structure of key hepatitis C virus proteins bound to three neutralizing antibodies.</li>
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<li>The findings provide new insights into how the virus invades cells and could inform development of vaccines or antiviral therapies</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="3D illustration of Hepatitis C virus">
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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/2022/20221108-hepititis-stock.jpg?itok=UPJkbvjo&timestamp=1667922750 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/2022/20221108-hepititis-stock.jpg?itok=zUt_fdqw&timestamp=1667922750 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/2022/20221108-hepititis-stock.jpg?itok=74bNrB18&timestamp=1667922750 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/2022/20221108-hepititis-stock.jpg?itok=blAlaTdW&timestamp=1667922750 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/2022/20221108-hepititis-stock.jpg?itok=iO8fEqlQ&timestamp=1667922750 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/2022/20221108-hepititis-stock.jpg?itok=zUt_fdqw&timestamp=1667922750" alt="3D illustration of Hepatitis C virus" title="3D illustration of Hepatitis C virus" />
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</picture><span class="caption">Effective vaccines against the Hepatitis C virus have proven elusive, in part because of the difficulty of deciphering the structures on its surface. </span><span class="credit">ART-ur / Shutterstock</span></div>
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||
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</div><p>Hepatitis C is a leading cause of long-term liver disease and liver cancer. Caused by a virus, it affects an estimated 58 million people worldwide. Hepatitis C is one of the most common blood-borne infections in the United States.</p>
|
||
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<p>Despite years of effort, researchers have not yet developed an effective vaccine that prevents infection. One obstacle has been that scientists only partly understand how the virus infects liver cells and evades antibodies.</p>
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||
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||
<p>Researchers have long known that the outer surface of the virus includes two envelope proteins called E1 and E2. These proteins unite to form a complex called E1E2. This protein complex blankets the outer surface of the virus and helps it enter liver cells, though the mechanism is unclear. As the only protein on the viral surface, the E1E2 assembly is also the main target for neutralizing antibodies.</p>
|
||
|
||
<p>Earlier studies have uncovered high-resolution structures for portions of E1 or E2 proteins. But detailed features of the E1E2 complex have been elusive, in part because the two isolated proteins form a fragile and flexible pairing that is difficult to view with high resolution.</p>
|
||
|
||
<p>An international research team led by Dr. Andrew B. Ward of Scripps Research Institute found a way to overcome this difficulty. The scientists discovered they could stabilize the entire E1E2 complex by including a neutralizing antibody. The antibody helps to stabilize the E1E2 complex in a more natural configuration. For subsequent analyses, the researchers added two more neutralizing antibodies.</p>
|
||
|
||
<p>They then used cryo-electron microscopy and advanced imaging software to look at structural details of E1E2 bound to the antibodies. This approach allowed the scientists to view the E1E2 complex, along with neutralizing antibodies, at near-atomic resolution. Their findings appeared in <em>Science</em> on October 21, 2022.</p>
|
||
|
||
<p>The structural analyses were generally consistent with earlier studies that examined portions of the viral proteins via X-ray crystallography. The team was able to model 51% of E1 and 82% of E2, including the crucial portions where they interact. The structure also disclosed previously unrecognized aspects of the bonds between the neutralizing antibodies and viral proteins.</p>
|
||
|
||
<p>In addition, the analysis exposed new details about the role of sugar-related molecules called glycans. Glycans help hide viruses from the immune system, and are a prominent component of the E1E2 complex. The glycans, the researchers found, not only help to mask viral regions that could be attacked by antibodies. They also play a stabilizing role by helping to hold the fragile E1E2 complex together.</p>
|
||
|
||
<p>The analysis sheds light on the structural changes that might allow the virus to fuse with and gain entry to liver cells. Such details could help guide development of structure-based vaccines and antiviral therapies.</p>
|
||
|
||
<p>“This long sought-after structural information on hepatitis C virus puts a wealth of previous observations into a structural context and paves the way for rational vaccine design against this incredibly difficult target,” Ward says.</p>
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||
<p>—by Vicki Contie</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/cells-maintain-repair-liver-identified" target="_top">Cells That Maintain and Repair the Liver Identified</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/signature-virus-exposure-may-help-detect-liver-cancer" target="_top">Signature of Virus Exposure May Help Detect Liver Cancer</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/hepatitis-c-virus-structure" target="_top">Hepatitis C Virus Structure </a></li><li><a href="https://newsinhealth.nih.gov/2014/03/your-liver-delivers" target="_top">Your Liver Delivers</a></li><li><a href="https://www.niddk.nih.gov/health-information/liver-disease/viral-hepatitis/hepatitis-c" target="_top">Hepatitis C</a></li><li><a href="https://www.niaid.nih.gov/diseases-conditions/hepatitis" target="_top">Hepatitis</a></li><li><a href="https://www.cdc.gov/hepatitis/hcv/" target="_top">Viral Hepatitis: Hepatitis C (CDC)</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/36264808/">Structure of the hepatitis C virus E1E2 glycoprotein complex.</a> Torrents de la Peña A, Sliepen K, Eshun-Wilson L, Newby ML, Allen JD, Zon I, Koekkoek S, Chumbe A, Crispin M, Schinkel J, Lander GC, Sanders RW, Ward AB. <em>Science</em>. 2022 Oct 21;378(6617):263-269. doi: 10.1126/science.abn9884. Epub 2022 Oct 20. PMID: 36264808.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of General Medical Sciences (NIGMS), National Science Foundation, Netherlands Organization for Scientific Research, Amsterdam Institute for Infection and Immunity, Bill & Melinda Gates Foundation.</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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