{"id":409,"date":"2014-06-03T15:14:29","date_gmt":"2014-06-03T19:14:29","guid":{"rendered":"http:\/\/med.virginia.edu\/membrane-biology\/?p=409"},"modified":"2024-01-11T15:58:19","modified_gmt":"2024-01-11T20:58:19","slug":"ebolas-fist-u-va-unlocks-how-deadly-virus-smashes-into-human-cells","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/membrane-biology\/ebolas-fist-u-va-unlocks-how-deadly-virus-smashes-into-human-cells\/","title":{"rendered":"Ebola\u2019s \u2018Fist\u2019: U.Va. Unlocks How Deadly Virus Smashes Into Human Cells"},"content":{"rendered":"

\"201405TammEbola-Story-UVAToday\"<\/a><\/p>\n

Researchers at the University of Virginia School of Medicine have discovered how the\u00a0deadly Ebola virus punches its way into the cytoplasm of cells. The finding identifies an\u00a0important target for blocking the infection process of this incurable disease that many fear\u00a0may be used for bioterror.\u00a0Outbreaks of this extremely dangerous, highly contagious virus are now under way in the\u00a0African countries of Guinea, Liberia and Sierra Leone. Ebola kills up to 90 percent of\u00a0people who contract it. In addition to the toll on human life in the areas already affected,\u00a0there is significant concern that it could spread elsewhere around the world, so finding\u00a0ways to combat it is a global priority.<\/p>\n

Understanding Ebola Infection<\/strong><\/p>\n

U.Va.\u2019s new discovery offers important insight into how the virus works its way into cells.\u00a0After the virus is engulfed by the cell, it is contained within a vesicle where it can do no\u00a0harm. But Ebola quickly escapes the vesicle, and now scientists understand how. U.Va.\u00a0researcher Lukas Tamm of the Department of Molecular Physiology and Biological\u00a0Physics and his team discovered that the pH level inside the vesicle triggers the surface\u00a0glycoprotein on the virus to form a \u201cfist\u201d that lets the virus punch its way into the cell\u2019s\u00a0cytoplasm, where it can effectively turn the cell into a factory for virus production.<\/p>\n

\u201cIf it stayed in the vesicle, it would be not much of a problem. The cell could digest it,\u201d\u00a0Tamm said. \u201cBut then it escapes from that internal vesicle into the body of the cell, and\u00a0that\u2019s when the danger happens. It does that by fusing its own membrane with that cellular\u00a0vesicle membrane, and that lets the RNA of the virus out into the cell to replicate, to\u00a0basically cause havoc in those cells.\u201d<\/p>\n

Unclenching the Fist<\/strong><\/p>\n

Ironically, when the virus approaches a cell, what becomes the fist looks more like an\u00a0outstretched hand. The U.Va. research explains how the virus forms its fist and identifies\u00a0amino acids within the virus critical for the clenching to occur. \u201cIf you lose those,\u201d Tamm\u00a0said, \u201cit would always be in the extended hand formation.\u201d<\/p>\n

To test his findings, Tamm turned to the School of Medicine\u2019s Judith M. White, a\u00a0researcher in the Department of Cell Biology who has developed virus-like particles that\u00a0act like Ebola, but pose no danger in the laboratory. Working with those particles, they\u00a0were able to verify Tamm\u2019s hypotheses about the fist-clenching process held true not just\u00a0in test tubes, but in live cells. Then they took the work even further, enlisting Dr. Peter M.\u00a0Kasson of the Department of Molecular Physiology and Biological Physics to create a\u00a0computer model of that process. The result is a remarkable new understanding of Ebola\u00a0infection.<\/p>\n

\u201cIt\u2019s a very nice collaboration between structural, cell and computational biologists that\u00a0shows how beneficial it is to have all these different areas of expertise here at U.Va., so\u00a0that we can tell more of the whole story,\u201d Tamm said.<\/p>\n

By understanding that story, researchers are a significant step closer to being able to stop\u00a0Ebola \u2013 and perhaps other viruses with similar structures as well.<\/p>\n

\u201cOnce you have visualized the molecular shape changes that these structures undergo\u00a0upon cell entry, you can see what molecules or potential anti-viral drugs could interfere\u00a0with this process,\u201d Tamm said. \u201cYou have these contacts that need to be made to make\u00a0the clenching of the fist happen \u2013 if you could find a molecule that throws a wrench into\u00a0the gears of that mechanism, you could actually block that from happening.\u201d<\/p>\n

Discovery Detailed<\/strong><\/p>\n

The researchers have detailed the fist-clenching process in a paper published by the\u00a0Journal of Virology. The article\u2019s authors are Sonia M. Gregory, Per Larsson, Elizabeth A.\u00a0Nelson, Kasson, White and Tamm.<\/p>\n

Source URL:\u00a0\u00a0https:\/\/news.virginia.edu\/content\/ebolas-fist-uva-unlocks-how-deadly-virus-smashes-human-cells<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers at the University of Virginia School of Medicine have discovered how the\u00a0deadly Ebola virus punches its way into the cytoplasm of cells. The finding identifies an\u00a0important target for blocking the infection process of this incurable disease that many fear\u00a0may be used for bioterror.\u00a0Outbreaks of this extremely dangerous, highly contagious virus are now under way […]<\/p>\n","protected":false},"author":431,"featured_media":410,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[1],"tags":[],"class_list":["post-409","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news"],"acf":false,"yoast_head":"\nEbola\u2019s \u2018Fist\u2019: U.Va. 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