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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2015-10-19T00:00:00-04:00" class="date-display-single">October 19, 2015</span></p><div class='syndicate'><h1>Dormant Viral Genes May Awaken to Cause ALS</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Ancient viral genes embedded in the human genome are reactivated in some patients with amyotrophic lateral sclerosis (ALS).</li>
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<li>The findings suggest that antiretroviral drugs, similar to those used for suppressing HIV, may be able to help some ALS patients.</li>
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<picture title="Mouse brain expressing env">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2015/20151019-ALS.jpg?itok=qfMPbpJg&timestamp=1445281406 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/2015/20151019-ALS.jpg?itok=t-pjCcfr&timestamp=1445281406 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/2015/20151019-ALS.jpg?itok=nm5--85R&timestamp=1445281406 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/2015/20151019-ALS.jpg?itok=l0d8ilhF&timestamp=1445281406 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/2015/20151019-ALS.jpg?itok=f07rO-OR&timestamp=1445281406 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2015/20151019-ALS.jpg?itok=t-pjCcfr&timestamp=1445281406" alt="Mouse brain expressing env." title="Mouse brain expressing env" />
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</picture><span class="caption">A mouse brain. Neurons (green) were genetically modified to produce a viral gene called env (red). Glial cells, a type of brain cell that supports neurons, are shown in purple, and nuclei of all cells are in blue. </span><span class="credit">Image courtesy of Nath lab, NINDS</span></div>
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</div><p>Currently, there’s no effective treatment for the more than 12,000 Americans with ALS. This fatal disorder destroys motor neurons—the nerve cells responsible for regulating voluntary muscles, such as those involved in speaking, walking, breathing, and swallowing. About 5-10% of all ALS cases are inherited. Most cases, though, are seemingly random, or “sporadic.”</p>
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<p>On rare occasions, HIV-infected AIDS patients develop ALS-like symptoms. HIV is a type of retrovirus, and when patients are treated with antiretroviral drugs, the ALS-like symptoms often subside. Previous studies have also detected the activity of reverse transcriptase—a protein encoded by retroviral genes—in the blood of some ALS patients. These findings suggest a possible connection between retroviruses and ALS.</p>
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<p>Human endogenous retroviruses (HERVs) leave genetic remnants of infection behind in human DNA. These genetic remains can be passed on for generations. They now make up nearly 8% of the human genome. Once thought to be inactive “junk” DNA, their role in health and disease has been little explored. A research team led by Dr. Avindra Nath of NIH’s National Institute of Neurological Disorders and Stroke (NINDS) set out to investigate the potential link between retroviruses and ALS. Their study was published in <em>Science Translational Medicine</em> on September 30, 2015.</p>
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<p>The researchers first examined brain samples from 10 patients with sporadic ALS. They found higher than normal levels of genes expressed from human endogenous retrovirus K (HERV-K). A protein encoded by a HERV-K gene called <em>env</em> was found in brain samples from ALS patients but not in healthy people or patients with Alzheimer’s disease. In laboratory experiments, activation of the full HERV-K genome or <em>env</em> alone killed healthy human neurons.</p>
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||
<p>The scientists next examined genetically modified mice whose neurons expressed the HERV-K <em>env</em> gene. The mice died earlier than normal and had problems with balance and walking that progressively worsened with age. When the scientists inspected the animals’ brains, spinal cords, and muscles, they found that only motor neurons—the cells that control movements and die in ALS—were damaged. Cells in other parts of the nervous system remained healthy.</p>
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<p>The scientists discovered that activation of HERV-K genes is controlled by TDP-43, a gene-regulating protein that was previously linked to ALS. This protein is known to control HIV production as well.</p>
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<p>The team is <a href="https://www.clinicaltrials.gov/ct2/show/NCT02437110" target="_blank">now collaborating</a> with researchers at Johns Hopkins University to study whether antiretroviral treatments can suppress HERV-K levels in patients with sporadic ALS. “We may have discovered a precision medicine solution for treating a neurodegenerative disorder,” Nath says.</p>
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</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/nuclear-pore-problems-may-lead-als-dementia" target="_top">Nuclear Pore Problems May Lead to ALS and Dementia</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/new-genetic-mutations-discovered-families-als" target="_top">New Genetic Mutations Discovered in Families with ALS</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/learning-how-support-cells-kill-nerve-cells-als" target="_top">Learning How Support Cells Kill Nerve Cells in ALS</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/misfolded-protein-clumps-common-dementia-lou-gehrigs-disease" target="_top">Misfolded Protein Clumps Common to Dementia, Lou Gehrig’s Disease</a></li><li><a href="https://newsinhealth.nih.gov/issue/aug2015/feature2" target="_top">All About ALS</a></li><li><a href="http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_ALS.htm" target="_top">Amyotrophic Lateral Sclerosis (ALS) Fact Sheet</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/26424568">Human endogenous retrovirus-K contributes to motor neuron disease.</a> Li W, Lee MH, Henderson L, Tyagi R, Bachani M, Steiner J, Campanac E, Hoffman DA, von Geldern G, Johnson K, Maric D, Morris HD, Lentz M, Pak K, Mammen A, Ostrow L, Rothstein J, Nath A. <em>Sci Transl Med.</em> 2015 Sep 30;7(307):307ra153. doi: 10.1126/scitranslmed.aac8201. PMID: 26424568.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH's National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); and the Robert Packard Center for ALS Research.</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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