{"id":7307,"date":"2016-07-14T20:00:09","date_gmt":"2016-07-14T18:00:09","guid":{"rendered":"http:\/\/news.embl.de\/?p=7307"},"modified":"2024-03-25T10:18:13","modified_gmt":"2024-03-25T09:18:13","slug":"1607-hiv-drugs","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/","title":{"rendered":"How new HIV drugs lock virus in immaturity"},"content":{"rendered":"\n

A new type of HIV drug currently being tested works in an unusual way, scientists in the Molecular Medicine Partnership Unit<\/a>, a collaboration between EMBL and Heidelberg University Hospital, have found. They also discovered that when the virus became resistant to early versions of these drugs, it did not do so by blocking or preventing their effects, but rather by circumventing them. The study, published online today in Science<\/em>, presents the most detailed view yet of part of the immature form of HIV.<\/p>\n\n\n\n

HIV, the virus that causes AIDS, comes in two forms: immature and mature. The immature form is assembled inside an infected person\u2019s cells. After an immature virus particle has left the cell, it has to change into the mature form before it can infect other human cells. A new group of drugs that inhibit this maturation is currently undergoing clinical trials, but so far it was unclear how exactly these drugs act.<\/p>\n\n\n\n

To go from immature to mature, HIV has to cut the connections between its main building blocks, and rearrange those pieces. John Briggs\u2019 lab<\/a> at EMBL and Hans-Georg Kr\u00e4usslich\u2019s lab<\/a> at Heidelberg University Hospital looked at a particularly important cutting point. It connects building blocks known as the capsid protein and the spacer peptide 1, and if it is not cut, the virus cannot mature. The scientists used a combination of cryo-electron tomography and subtomogram averaging to reveal exactly what this part of the immature form of HIV looks like in 3D. They found that the cutting site is hidden in a position where the virus\u2019 cutting machinery can\u2019t sever it. So for the virus to mature, the structure first has to change, to expose that cutting point.<\/p>\n\n\n\n

\u201cWhen we looked at the virus with one of these inhibitor drugs on it, we found that the inhibitor doesn\u2019t prevent the cutting machinery from getting in, as you might expect,\u201d says Florian Schur, who carried out the work in Briggs\u2019 lab. \u201cRather, the drug locks the immature virus structure in place, so that it can\u2019t be cut.\u201d<\/p>\n\n\n\n

\"The<\/a>
The scientists determined the cutting site’s 3D structure in whole HIV particles. IMAGE: Florian Schur\/EMBL<\/figcaption><\/figure><\/div>\n\n\n\n

When the new inhibitor drugs were first developed, scientists found that HIV viruses with certain mutations in their genetic sequence were unaffected by the drugs \u2013 they were resistant. Having determined what the cutting point looks like and how the drugs act, Briggs and colleagues are now able to understand the effects of those mutations.<\/p>\n\n\n\n

\u201cRather than stopping the drug from binding, the virus becomes resistant through mutations that destabilise the immature structure,\u201d says Kr\u00e4usslich. \u201cThis allows it to rearrange and be cut even when the drug is in place.\u201d<\/p>\n\n\n\n

The researchers would now like to probe the virus and the inhibitor drugs in even greater detail, to understand exactly how the drugs attach themselves to the viral proteins, and potentially gather data that could help to search for better drugs \u2013 or to design them.<\/p>\n\n\n\n

The method used in this study \u2013 combined cryo-electron tomography and subtomogram averaging \u2013 enables scientists to study structures inside irregular viruses like HIV, or within cells. In essence, the scientists use an electron microscope to obtain a 3D image of the sample \u2013 in this case, whole HIV-1 particles. They then identify all the copies of the object they want to study \u2013 all the instances of the capsid protein-spacer peptide 1 cutting point \u2013 and use software to rotate the 3D image of each copy so that they are all facing the same way. By repeating this procedure with thousands of images, the scientists can obtain an accurate picture. With this approach, researchers can study such samples without having to purify them in a test-tube, which means that they see them in their real state. The EMBL scientists\u2019 work now proves that the method can provide the level of detail that is crucial to understanding how molecular machines work and to informing drug design.<\/p>\n","protected":false},"excerpt":{"rendered":"

Study provides insights into workings of new HIV drugs and how virus becomes resistant<\/p>\n","protected":false},"author":8,"featured_media":7310,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[348,32,43,79,25,1748,35],"embl_taxonomy":[],"class_list":["post-7307","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-briggs","tag-health","tag-heidelberg","tag-microscopy","tag-partnerships","tag-press-release","tag-structural-biology"],"acf":{"article_intro":"

Study provides insights into workings of new HIV drugs and how virus becomes resistant<\/p>\n","related_links":[{"link_description":"Also published as an EMBL Press Release","link_url":"http:\/\/s.embl.org\/pr140716"},{"link_description":"German version (Heidelberg University Hospital)","link_url":"https:\/\/www.klinikum.uni-heidelberg.de\/pressemitteilungen.136514.0.html?ifab_modus=detail&ifab_id=5393"},{"link_description":"Briggs lab's previous work on HIV","link_url":"http:\/\/news.embl.de\/science\/1411_hiv\/"},{"link_description":"Molecular Medicine Partnership Unit","link_url":"http:\/\/www.embl.de\/research\/partnerships\/local\/mmpu\/"},{"link_description":"Briggs lab at EMBL","link_url":"http:\/\/www.embl.de\/research\/units\/scb\/briggs\/"},{"link_description":"Kr\u00e4usslich lab at Heidelberg University Hospital","link_url":"https:\/\/www.klinikum.uni-heidelberg.de\/Kraeusslich.6551.0.html"}],"article_sources":[{"source_description":"

Schur FKM et al.<\/em> Science<\/em>, 14 July 2016. DOI: 10.1126\/science.aaf9620<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1126\/science.aaf9620"}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"\nHow new HIV drugs lock virus in immaturity<\/title>\n<meta name=\"description\" content=\"Study reveals how new HIV drugs prevent virus from maturing, and how the virus becomes resistant to those drugs\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How new HIV drugs lock virus in immaturity\" \/>\n<meta property=\"og:description\" content=\"Study reveals how new HIV drugs prevent virus from maturing, and how the virus becomes resistant to those drugs\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2016-07-14T18:00:09+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-25T09:18:13+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/07\/pr14jul16-ib.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Sonia Furtado Neves\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@Aur_ora\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Sonia Furtado Neves\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\"},\"author\":{\"name\":\"Sonia Furtado Neves\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/d926199a955624b44dda296f396c5e68\"},\"headline\":\"How new HIV drugs lock virus in immaturity\",\"datePublished\":\"2016-07-14T18:00:09+00:00\",\"dateModified\":\"2024-03-25T09:18:13+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\"},\"wordCount\":666,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/07\/pr14jul16-ib.jpg\",\"keywords\":[\"briggs\",\"health\",\"heidelberg\",\"microscopy\",\"partnerships\",\"press release\",\"structural biology\"],\"articleSection\":[\"Science\",\"Science & Technology\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\",\"url\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\",\"name\":\"How new HIV drugs lock virus in immaturity\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/07\/pr14jul16-ib.jpg\",\"datePublished\":\"2016-07-14T18:00:09+00:00\",\"dateModified\":\"2024-03-25T09:18:13+00:00\",\"description\":\"Study reveals how new HIV drugs prevent virus from maturing, and how the virus becomes resistant to those drugs\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1607-hiv-drugs\/#primaryimage\",\"url\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/07\/pr14jul16-ib.jpg\",\"contentUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/07\/pr14jul16-ib.jpg\",\"width\":620,\"height\":425,\"caption\":\"For HIV to mature, a crucial cutting point has to be exposed. 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