National Institute of Allergy and Infectious DiseasesNational Institute of Allergy and Infectious Diseases
AIDS Researchers Unlock Cell Death Mystery
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Warner,2","publishDate":1292287381,"status":"inherit","parent":10853,"modified":1292287381,"caption":null,"credit":null,"description":"\u003cp class=\"attachment\">\u003ca href='http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/12/Gilad-Warner22.jpg' title='Gilad - Warner,2'>\u003cimg width=\"300\" height=\"200\" src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/12/Gilad-Warner22.jpg\" class=\"attachment-medium\" alt=\"Gilad - Warner,2\" title=\"Gilad - Warner,2\" />\u003c/a>\u003c/p>","imgSizes":{"guest-author-32":{"file":"https://ww2.kqed.org/app/uploads/sites/39/2010/12/Gilad-Warner22-32x32.jpg","width":32,"height":32,"mimeType":"image/jpeg"},"guest-author-64":{"file":"https://ww2.kqed.org/app/uploads/sites/39/2010/12/Gilad-Warner22-64x64.jpg","width":64,"height":64,"mimeType":"image/jpeg"},"guest-author-96":{"file":"https://ww2.kqed.org/app/uploads/sites/39/2010/12/Gilad-Warner22-96x96.jpg","width":96,"height":96,"mimeType":"image/jpeg"},"guest-author-128":{"file":"https://ww2.kqed.org/app/uploads/sites/39/2010/12/Gilad-Warner22-128x128.jpg","width":128,"height":128,"mimeType":"image/jpeg"},"detail":{"file":"https://ww2.kqed.org/app/uploads/sites/39/2010/12/Gilad-Warner22-75x75.jpg","width":75,"height":75,"mimeType":"image/jpeg"},"kqedFullSize":{"file":"https://ww2.kqed.org/app/uploads/sites/39/2010/12/Gilad-Warner22.jpg","width":300,"height":200}},"fetchFailed":false,"isLoading":false}},"audioPlayerReducer":{"postId":"stream_live"},"authorsReducer":{"sheraz-sadiq":{"type":"authors","id":"6176","meta":{"index":"authors_1591205172","id":"6176","found":true},"name":"Sheraz Sadiq","firstName":"Sheraz","lastName":"Sadiq","slug":"sheraz-sadiq","email":"ssadiq@kqed.org","display_author_email":false,"staff_mastheads":[],"title":null,"bio":"Sheraz Sadiq is an Emmy Award-winning producer at San Francisco PBS affiliate KQED. 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In addition to producing television content for KQED Science, he has also created online features and written news articles on scientific subjects ranging from astronomy to synthetic biology.","avatar":"https://secure.gravatar.com/avatar/9731b29e144af1965b0b7eaa56555561?s=600&d=blank&r=g","twitter":null,"facebook":null,"instagram":null,"linkedin":null,"sites":[{"site":"arts","roles":["editor"]},{"site":"quest","roles":["leadcoordinator","editor"]}],"headData":{"title":"Sheraz Sadiq | KQED","description":null,"ogImgSrc":"https://secure.gravatar.com/avatar/9731b29e144af1965b0b7eaa56555561?s=600&d=blank&r=g","twImgSrc":"https://secure.gravatar.com/avatar/9731b29e144af1965b0b7eaa56555561?s=600&d=blank&r=g"},"isLoading":false,"link":"/author/sheraz-sadiq"}},"breakingNewsReducer":{},"campaignFinanceReducer":{},"firebase":{"requesting":{},"requested":{},"timestamps":{},"data":{},"ordered":{},"auth":{"isLoaded":false,"isEmpty":true},"authError":null,"profile":{"isLoaded":false,"isEmpty":true},"listeners":{"byId":{},"allIds":[]},"isInitializing":false,"errors":[]},"navBarReducer":{"navBarId":"home","fullView":true,"showPlayer":false},"navMenuReducer":{"menus":[{"key":"menu1","items":[{"name":"News","link":"/","type":"title"},{"name":"Politics","link":"/politics"},{"name":"Science","link":"/science"},{"name":"Education","link":"/educationnews"},{"name":"Housing","link":"/housing"},{"name":"Immigration","link":"/immigration"},{"name":"Criminal Justice","link":"/criminaljustice"},{"name":"Silicon Valley","link":"/siliconvalley"},{"name":"Forum","link":"/forum"},{"name":"The California Report","link":"/californiareport"}]},{"key":"menu2","items":[{"name":"Arts & Culture","link":"/arts","type":"title"},{"name":"Critics’ Picks","link":"/thedolist"},{"name":"Cultural Commentary","link":"/artscommentary"},{"name":"Food & Drink","link":"/food"},{"name":"Bay Area Hip-Hop","link":"/bayareahiphop"},{"name":"Rebel Girls","link":"/rebelgirls"},{"name":"Arts Video","link":"/artsvideos"}]},{"key":"menu3","items":[{"name":"Podcasts","link":"/podcasts","type":"title"},{"name":"Bay Curious","link":"/podcasts/baycurious"},{"name":"Rightnowish","link":"/podcasts/rightnowish"},{"name":"The Bay","link":"/podcasts/thebay"},{"name":"On Our Watch","link":"/podcasts/onourwatch"},{"name":"Mindshift","link":"/podcasts/mindshift"},{"name":"Consider This","link":"/podcasts/considerthis"},{"name":"Political Breakdown","link":"/podcasts/politicalbreakdown"}]},{"key":"menu4","items":[{"name":"Live Radio","link":"/radio","type":"title"},{"name":"TV","link":"/tv","type":"title"},{"name":"Events","link":"/events","type":"title"},{"name":"For Educators","link":"/education","type":"title"},{"name":"Support KQED","link":"/support","type":"title"},{"name":"About","link":"/about","type":"title"},{"name":"Help Center","link":"https://kqed-helpcenter.kqed.org/s","type":"title"}]}]},"pagesReducer":{},"postsReducer":{"stream_live":{"type":"live","id":"stream_live","audioUrl":"https://streams.kqed.org/kqedradio","title":"Live Stream","excerpt":"Live Stream information currently unavailable.","link":"/radio","featImg":"","label":{"name":"KQED Live","link":"/"}},"stream_kqedNewscast":{"type":"posts","id":"stream_kqedNewscast","audioUrl":"https://www.kqed.org/.stream/anon/radio/RDnews/newscast.mp3?_=1","title":"KQED Newscast","featImg":"","label":{"name":"88.5 FM","link":"/"}},"quest_10853":{"type":"posts","id":"quest_10853","meta":{"index":"posts_1591205157","site":"quest","id":"10853","score":null,"sort":[1291224354000]},"guestAuthors":[],"slug":"aids-researchers-unlock-cell-death-mystery","title":"AIDS Researchers Unlock Cell Death Mystery","publishDate":1291224354,"format":"standard","headTitle":"QUEST | KQED Science","labelTerm":{"site":"quest"},"content":"\u003cp>\u003cspan class=\"left\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/12/Gilad-Warner211.jpg\" alt=\"\">\u003c/a>\u003cem>HIV researcher Gilad Doitsh talks with Dr. Warner Greene (seated) at the Gladstone Institute of Virology and Immunology in San Francisco. (Credit: Chris Goodfellow, Gladstone Institutes) \u003c/em>\u003c/span>\u003c/p>\n\u003cp>\u003cem>Reported for \u003ca href=\"http://www.kqed.org/news/\">KQEDnews.org\u003c/a>.\u003c/em>\u003c/p>\n\u003cp>For nearly 30 years scientists have known that a cell vital to the immune system dies off in patients with HIV, leading eventually to the onset of AIDS. But exactly when and how has remained a mystery - until now. \u003c/p>\n\u003cp>Researchers at the \u003ca href=\"http://www.gladstone.ucsf.edu/gladstone/site/givi/\">Gladstone Institute of Virology and Immunology\u003c/a> in San Francisco showed that the overwhelming majority of the cells die not from HIV, the virus that causes AIDS, but rather from the cell’s own defensive response to HIV even before the virus can make copies of itself. \u003c/p>\n\u003cp>The new insights may one day lead to new, more effective drugs to treat HIV. \u003c/p>\n\u003cp>[ad fullwidth]\u003c/p>\n\u003cp>\u003c!--more-->\u003c/p>\n\u003cp>“The cells understand they've been attacked and they commit suicide,” said Gilad Doitsh, a research scientist and the lead author of the study, which was published last Wednesday in the scientific journal \u003cem>\u003ca href=\"http://www.cell.com/fulltext/S0092-8674%2810%2901245-6\">Cell\u003c/a>\u003c/em>.\u003c/p>\n\u003cp>“It’s as though the virus needs to go through several rooms of the cell without activating the alarm,” he said, “and if it stalls in one of those rooms, the alarm sounds and the cell kills itself.” \u003c/p>\n\u003cp>\u003cspan class=\"right\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/11/GladstoneInstituteVirologyImmunology_Doitsh-21.jpg\" alt=\"\">\u003c/a>\u003cem>Gilad Doitsh, a molecular biologist at the Gladstone Institute of Virology and Immunology in San Francisco, studies the HIV virus. (Credit: Chris Goodfellow, Gladstone Institutes)\u003c/em>\u003c/span>\u003c/p>\n\u003cp>Doitsh and his colleagues, working at the University of California-San Francisco’s Mission Bay campus, focused their research on a type of white blood cells called 'CD4 T cells'. The cells play a critical role in fighting infection from bacteria and viruses. \u003c/p>\n\u003cp>CD4 T cells are also known as ‘helper cells’ because they help the production of a specific immune response – antibodies – to a specific bacteria or virus. After a bacteria or virus enters the body, communication occurs between different immune cells in the lymph tissues to develop an antibody which the immune system will then remember and reproduce if it encounters the same type of bacteria or virus weeks, months or even years later. \u003c/p>\n\u003cp>Though the human body has 10 types of immune cells, the main target of HIV is CD4 T cells. But despite this limited target, the immune system still can’t produce an antibody to marshal an effective, one-size-fits-all attack against the virus. \u003c/p>\n\u003cp>\"The major challenge of HIV is its ability to mutate or change. So we're constantly chasing the virus,” said Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology and a senior author of the study. \"It requires combination antiretroviral therapy to attack it. Single drugs will not work,” he added. \u003c/p>\n\u003cp>At least 26 drugs have been approved by the FDA to treat HIV, which infects roughly 60,000 people in the U.S. each year. Worldwide, more than 33 million people are living with HIV, with 10 million of them awaiting drug treatment, according to the \u003ca href=\"http://www.unaids.org/GlobalReport/default.htm\">United Nations\u003c/a>. \u003c/p>\n\u003cp>Doitsh’s team takes an unusually thorough approach when investigating the spread of HIV in the human body. \u003c/p>\n\u003cp>“Our lab is very, very unique. We process human tissues from the tonsils, spleen, cervix, skin, colon, blood, semen - any tissue where HIV multiplies or that serves as a vehicle to transmit HIV from person to person,” he said. “You see the virus behave differently depending on the tissue it has infected.” \u003c/p>\n\u003cp>According to Doitsh, most other labs researching HIV and AIDS study the virus in blood because of the ease of finding copies of the virus there, even though it’s not the site where the virus actually replicates, or makes copies, of itself. So Doitsh used tonsil and spleen tissues because they’re the principal places where the virus replicates. Being lymph organs, the tonsil and spleen also contain large amounts of CD4 T cells.\u003c/p>\n\u003cp>The researchers exposed the tonsil and spleen tissues to HIV. Then, to tell when the virus was actively replicating in the CD4 T cells, the scientists used a marker which turned green when the virus had fully hijacked the genetic machinery of the cell, tricking the cell into making thousands of new copies of the virus. \u003c/p>\n\u003cp>After binding to the CD4 T cell, the virus can’t directly enter the cell’s nucleus to take over its DNA, the genetic program which runs the cell. And since the virus doesn’t have DNA of its own, it has to convert its RNA, the genetic program on which it runs, to DNA in a process called ‘reverse transcription’. \u003c/p>\n\u003cp>When it has converted its RNA to DNA, HIV can then speak the genetic language of the CD4 T cell. It enters the infected cell’s nucleus and boots up its genetic program, which instructs the cell to make new copies of the virus, thereby amplifying HIV in the body. \u003c/p>\n\u003cp>And although all the CD4 T cells eventually died from infection by the virus, how they died was a bit of a surprise.\u003c/p>\n\u003cp>Only about 5 percent of the cells that died were \"productively\", or fully, infected with HIV. The other 95 percent “bystander” cells died not from the virus itself but from an alarm signal inside the cell which triggered it to commit suicide after it was exposed to the virus but before the virus could replicate inside it. \u003c/p>\n\u003cp>“These CD4 T cells commit suicide to protect the body, but you can't have all the soldiers commit suicide because then the country has no more army,” said Doitsh. \u003c/p>\n\u003cp>\u003cspan class=\"left\">\u003ca href=\"http://www.gladstone.ucsf.edu/gladstone/files/publicaffairs/DoitshCellCycle112410.jpg\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/11/GladstoneInstituteVirologyImmunology_DoitshCellCycle112410-22.jpg\" alt=\"\">\u003c/a>\u003cem>Graphic showing to the left, a CD4 T cell that commits suicide after infection by HIV, whereas the illustration on the right depicts a cell that allows HIV to replicate in it. (Click on image for a larger version) (Credit: Gilad Doitsh, Gladstone Institute of Virology and Immunology)\u003c/em>\u003c/span>\u003c/p>\n\u003cp>To figure out exactly when these CD4 T cell ‘soldiers’ committed suicide, Doitsh exposed the CD4 T cells to different antiretroviral drugs like AZT, AMD3100 and T20, which attack the virus at various stages of its life cycle. \u003c/p>\n\u003cp>While AZT failed to rescue the infected CD4 T cells from dying, the other drugs were able to save the CD4 T cells because they attacked the virus before it entered the nucleus of the cell. But Doitsh and his colleagues didn’t know if the cells were committing suicide early on, when the virus merely touched the cell to enter it, or later, when the virus had already entered the cell. \u003c/p>\n\u003cp>So they used another drug, Efavirenz, which attacks HIV after it has entered the cell but before it starts making copies of itself from within the cell’s nucleus. When the CD4 T cells were exposed to Efavirenz, they survived. \u003c/p>\n\u003cp>“People thought that the virus could be on the outside of the cell, that it’s enough to put the key into the lock to signal the destruction of the room,” said Doitsh. “We showed that it’s not the key in the lock but that the virus has to actually go inside the room - or the cell - for the cell to die.” \u003c/p>\n\u003cp>“It hasn't been very clear why these so-called ‘bystander cells’ also die,” said Tae-Wook Chun, a staff scientist who has been studying HIV for 12 years at the \u003ca href=\"http://www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx\">National Institute of Allergy and Infectious Diseases\u003c/a> in Bethesda, Maryland. “The researchers found that these cells also get infected, although HIV doesn’t complete its life cycle in these cells. So they solved one of the mysteries in HIV research,” he added. \u003c/p>\n\u003cp>But that’s not all they found.\u003c/p>\n\u003cp>“The second huge surprise we found was that the mechanism of cell death was not a silent one. These cells do not go silently into the night,” said Greene.\u003c/p>\n\u003cp>Instead, Greene said they died a “fiery death,” causing “significant inflammation” as they erupted their cellular contents and released a chemical signal which recruited healthy CD4 T cells to the site of infection. \u003c/p>\n\u003cp>“It’s like a 911 call, with the dying cell saying, ‘we need more white blood cells to fight whatever infection is going on’” said Doitsh. “The new CD4 T cells want to help but HIV is there,” he added. \u003c/p>\n\u003cp>“It’s a vicious cycle, whereby the dying CD4 T cells release inflammatory signals that attract more cells to die,” said Greene. \u003c/p>\n\u003cp>This inflammatory response the researchers observed offers an interesting avenue to explore for the possible development of more effective HIV drugs.\u003c/p>\n\u003cp>“I think there are possibilities that we could block the inflammation component and therefore greatly modify the progression of disease,” said Greene. He also pointed out that primates like chimpanzees who are infected with a strain of HIV experience a drop in CD4 T cells but they don’t show signs of inflammation, nor crucially, do they develop AIDS. \u003c/p>\n\u003cp>Tae-Wook Chun at NIAID, however, cautioned that additional studies need to be done, perhaps with tissue from already infected HIV patients, to determine the clinical relevance of the findings. \u003c/p>\n\u003cp>The scientists will next try to track down the cellular sensor which detects HIV in the cell body and triggers the cellular suicide. They also want to study the virus to see if it has genes which allow it to turn off the cellular sensor in that small percentage of cells which become a host for making additional copies of the virus.\u003c/p>\n\u003cp>\u003cspan class=\"right\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/11/GladstoneInstituteVirologyImmunology_scientist-21.jpg\" alt=\"\">\u003c/a>\u003cem>HIV researcher Mauricio Montano at work at the Gladstone Institute of Virology and Immunology. (Credit: Chris Goodfellow, Gladstone Institutes) \u003c/em>\u003c/span>\u003c/p>\n\u003cp>Gilad Doitsh spent seven years doing the research in Greene’s lab and confirming his results before he was confident enough to present his findings for publication. Today, he advises three doctoral students who are beginning to investigate the behavior of HIV, much like he did nearly a decade ago. \u003c/p>\n\u003cp>“I tell them we are like detectives,” said Doitsh. “We have a suspect – HIV. We’re sure he committed murder but we have to collect the best evidence to convince the jury so that this guy can go to jail.” \u003c/p>\n\u003cp>“You have to know every aspect of HIV. You take baby steps but if every step is solid, then you have enough proof to convict the suspect,” he added. \u003c/p>\n\u003cp>[ad floatright]\u003c/p>\n\u003cp> 37.767050 -122.391139\u003c/p>\n\n","blocks":[],"excerpt":"For nearly 30 years scientists have known that a cell vital to the immune system dies off in patients with HIV, leading eventually to the onset of AIDS. But exactly when and how has remained a mystery - until now.","status":"publish","parent":0,"modified":1316922397,"stats":{"hasAudio":false,"hasVideo":false,"hasChartOrMap":false,"iframeSrcs":[],"hasGoogleForm":false,"hasGallery":false,"hasHearkenModule":false,"hasPolis":false,"paragraphCount":45,"wordCount":1777},"headData":{"title":"AIDS Researchers Unlock Cell Death Mystery | KQED","description":"For nearly 30 years scientists have known that a cell vital to the immune system dies off in patients with HIV, leading eventually to the onset of AIDS. But exactly when and how has remained a mystery - until now.","ogTitle":"","ogDescription":"","ogImgId":"","twTitle":"","twDescription":"","twImgId":""},"disqusIdentifier":"10853 http://www.kqed.org/quest/blog/2010/12/01/tiny-satellites-give-nasa-big-returns-2/","disqusUrl":"https://ww2.kqed.org/quest/2010/12/01/aids-researchers-unlock-cell-death-mystery/","disqusTitle":"AIDS Researchers Unlock Cell Death Mystery","path":"/quest/10853/aids-researchers-unlock-cell-death-mystery","audioTrackLength":null,"parsedContent":[{"type":"contentString","content":"\u003cdiv class=\"post-body\">\u003cp>\u003cp>\u003cspan class=\"left\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/12/Gilad-Warner211.jpg\" alt=\"\">\u003c/a>\u003cem>HIV researcher Gilad Doitsh talks with Dr. Warner Greene (seated) at the Gladstone Institute of Virology and Immunology in San Francisco. (Credit: Chris Goodfellow, Gladstone Institutes) \u003c/em>\u003c/span>\u003c/p>\n\u003cp>\u003cem>Reported for \u003ca href=\"http://www.kqed.org/news/\">KQEDnews.org\u003c/a>.\u003c/em>\u003c/p>\n\u003cp>For nearly 30 years scientists have known that a cell vital to the immune system dies off in patients with HIV, leading eventually to the onset of AIDS. But exactly when and how has remained a mystery - until now. \u003c/p>\n\u003cp>Researchers at the \u003ca href=\"http://www.gladstone.ucsf.edu/gladstone/site/givi/\">Gladstone Institute of Virology and Immunology\u003c/a> in San Francisco showed that the overwhelming majority of the cells die not from HIV, the virus that causes AIDS, but rather from the cell’s own defensive response to HIV even before the virus can make copies of itself. \u003c/p>\n\u003cp>The new insights may one day lead to new, more effective drugs to treat HIV. \u003c/p>\n\u003cp>\u003c/p>\u003c/div>","attributes":{"named":{},"numeric":[]}},{"type":"component","content":"","name":"ad","attributes":{"named":{"label":"fullwidth"},"numeric":["fullwidth"]}},{"type":"contentString","content":"\u003cdiv class=\"post-body\">\u003cp>\u003c/p>\n\u003cp>\u003c!--more-->\u003c/p>\n\u003cp>“The cells understand they've been attacked and they commit suicide,” said Gilad Doitsh, a research scientist and the lead author of the study, which was published last Wednesday in the scientific journal \u003cem>\u003ca href=\"http://www.cell.com/fulltext/S0092-8674%2810%2901245-6\">Cell\u003c/a>\u003c/em>.\u003c/p>\n\u003cp>“It’s as though the virus needs to go through several rooms of the cell without activating the alarm,” he said, “and if it stalls in one of those rooms, the alarm sounds and the cell kills itself.” \u003c/p>\n\u003cp>\u003cspan class=\"right\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/11/GladstoneInstituteVirologyImmunology_Doitsh-21.jpg\" alt=\"\">\u003c/a>\u003cem>Gilad Doitsh, a molecular biologist at the Gladstone Institute of Virology and Immunology in San Francisco, studies the HIV virus. (Credit: Chris Goodfellow, Gladstone Institutes)\u003c/em>\u003c/span>\u003c/p>\n\u003cp>Doitsh and his colleagues, working at the University of California-San Francisco’s Mission Bay campus, focused their research on a type of white blood cells called 'CD4 T cells'. The cells play a critical role in fighting infection from bacteria and viruses. \u003c/p>\n\u003cp>CD4 T cells are also known as ‘helper cells’ because they help the production of a specific immune response – antibodies – to a specific bacteria or virus. After a bacteria or virus enters the body, communication occurs between different immune cells in the lymph tissues to develop an antibody which the immune system will then remember and reproduce if it encounters the same type of bacteria or virus weeks, months or even years later. \u003c/p>\n\u003cp>Though the human body has 10 types of immune cells, the main target of HIV is CD4 T cells. But despite this limited target, the immune system still can’t produce an antibody to marshal an effective, one-size-fits-all attack against the virus. \u003c/p>\n\u003cp>\"The major challenge of HIV is its ability to mutate or change. So we're constantly chasing the virus,” said Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology and a senior author of the study. \"It requires combination antiretroviral therapy to attack it. Single drugs will not work,” he added. \u003c/p>\n\u003cp>At least 26 drugs have been approved by the FDA to treat HIV, which infects roughly 60,000 people in the U.S. each year. Worldwide, more than 33 million people are living with HIV, with 10 million of them awaiting drug treatment, according to the \u003ca href=\"http://www.unaids.org/GlobalReport/default.htm\">United Nations\u003c/a>. \u003c/p>\n\u003cp>Doitsh’s team takes an unusually thorough approach when investigating the spread of HIV in the human body. \u003c/p>\n\u003cp>“Our lab is very, very unique. We process human tissues from the tonsils, spleen, cervix, skin, colon, blood, semen - any tissue where HIV multiplies or that serves as a vehicle to transmit HIV from person to person,” he said. “You see the virus behave differently depending on the tissue it has infected.” \u003c/p>\n\u003cp>According to Doitsh, most other labs researching HIV and AIDS study the virus in blood because of the ease of finding copies of the virus there, even though it’s not the site where the virus actually replicates, or makes copies, of itself. So Doitsh used tonsil and spleen tissues because they’re the principal places where the virus replicates. Being lymph organs, the tonsil and spleen also contain large amounts of CD4 T cells.\u003c/p>\n\u003cp>The researchers exposed the tonsil and spleen tissues to HIV. Then, to tell when the virus was actively replicating in the CD4 T cells, the scientists used a marker which turned green when the virus had fully hijacked the genetic machinery of the cell, tricking the cell into making thousands of new copies of the virus. \u003c/p>\n\u003cp>After binding to the CD4 T cell, the virus can’t directly enter the cell’s nucleus to take over its DNA, the genetic program which runs the cell. And since the virus doesn’t have DNA of its own, it has to convert its RNA, the genetic program on which it runs, to DNA in a process called ‘reverse transcription’. \u003c/p>\n\u003cp>When it has converted its RNA to DNA, HIV can then speak the genetic language of the CD4 T cell. It enters the infected cell’s nucleus and boots up its genetic program, which instructs the cell to make new copies of the virus, thereby amplifying HIV in the body. \u003c/p>\n\u003cp>And although all the CD4 T cells eventually died from infection by the virus, how they died was a bit of a surprise.\u003c/p>\n\u003cp>Only about 5 percent of the cells that died were \"productively\", or fully, infected with HIV. The other 95 percent “bystander” cells died not from the virus itself but from an alarm signal inside the cell which triggered it to commit suicide after it was exposed to the virus but before the virus could replicate inside it. \u003c/p>\n\u003cp>“These CD4 T cells commit suicide to protect the body, but you can't have all the soldiers commit suicide because then the country has no more army,” said Doitsh. \u003c/p>\n\u003cp>\u003cspan class=\"left\">\u003ca href=\"http://www.gladstone.ucsf.edu/gladstone/files/publicaffairs/DoitshCellCycle112410.jpg\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/11/GladstoneInstituteVirologyImmunology_DoitshCellCycle112410-22.jpg\" alt=\"\">\u003c/a>\u003cem>Graphic showing to the left, a CD4 T cell that commits suicide after infection by HIV, whereas the illustration on the right depicts a cell that allows HIV to replicate in it. (Click on image for a larger version) (Credit: Gilad Doitsh, Gladstone Institute of Virology and Immunology)\u003c/em>\u003c/span>\u003c/p>\n\u003cp>To figure out exactly when these CD4 T cell ‘soldiers’ committed suicide, Doitsh exposed the CD4 T cells to different antiretroviral drugs like AZT, AMD3100 and T20, which attack the virus at various stages of its life cycle. \u003c/p>\n\u003cp>While AZT failed to rescue the infected CD4 T cells from dying, the other drugs were able to save the CD4 T cells because they attacked the virus before it entered the nucleus of the cell. But Doitsh and his colleagues didn’t know if the cells were committing suicide early on, when the virus merely touched the cell to enter it, or later, when the virus had already entered the cell. \u003c/p>\n\u003cp>So they used another drug, Efavirenz, which attacks HIV after it has entered the cell but before it starts making copies of itself from within the cell’s nucleus. When the CD4 T cells were exposed to Efavirenz, they survived. \u003c/p>\n\u003cp>“People thought that the virus could be on the outside of the cell, that it’s enough to put the key into the lock to signal the destruction of the room,” said Doitsh. “We showed that it’s not the key in the lock but that the virus has to actually go inside the room - or the cell - for the cell to die.” \u003c/p>\n\u003cp>“It hasn't been very clear why these so-called ‘bystander cells’ also die,” said Tae-Wook Chun, a staff scientist who has been studying HIV for 12 years at the \u003ca href=\"http://www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx\">National Institute of Allergy and Infectious Diseases\u003c/a> in Bethesda, Maryland. “The researchers found that these cells also get infected, although HIV doesn’t complete its life cycle in these cells. So they solved one of the mysteries in HIV research,” he added. \u003c/p>\n\u003cp>But that’s not all they found.\u003c/p>\n\u003cp>“The second huge surprise we found was that the mechanism of cell death was not a silent one. These cells do not go silently into the night,” said Greene.\u003c/p>\n\u003cp>Instead, Greene said they died a “fiery death,” causing “significant inflammation” as they erupted their cellular contents and released a chemical signal which recruited healthy CD4 T cells to the site of infection. \u003c/p>\n\u003cp>“It’s like a 911 call, with the dying cell saying, ‘we need more white blood cells to fight whatever infection is going on’” said Doitsh. “The new CD4 T cells want to help but HIV is there,” he added. \u003c/p>\n\u003cp>“It’s a vicious cycle, whereby the dying CD4 T cells release inflammatory signals that attract more cells to die,” said Greene. \u003c/p>\n\u003cp>This inflammatory response the researchers observed offers an interesting avenue to explore for the possible development of more effective HIV drugs.\u003c/p>\n\u003cp>“I think there are possibilities that we could block the inflammation component and therefore greatly modify the progression of disease,” said Greene. He also pointed out that primates like chimpanzees who are infected with a strain of HIV experience a drop in CD4 T cells but they don’t show signs of inflammation, nor crucially, do they develop AIDS. \u003c/p>\n\u003cp>Tae-Wook Chun at NIAID, however, cautioned that additional studies need to be done, perhaps with tissue from already infected HIV patients, to determine the clinical relevance of the findings. \u003c/p>\n\u003cp>The scientists will next try to track down the cellular sensor which detects HIV in the cell body and triggers the cellular suicide. They also want to study the virus to see if it has genes which allow it to turn off the cellular sensor in that small percentage of cells which become a host for making additional copies of the virus.\u003c/p>\n\u003cp>\u003cspan class=\"right\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/11/GladstoneInstituteVirologyImmunology_scientist-21.jpg\" alt=\"\">\u003c/a>\u003cem>HIV researcher Mauricio Montano at work at the Gladstone Institute of Virology and Immunology. (Credit: Chris Goodfellow, Gladstone Institutes) \u003c/em>\u003c/span>\u003c/p>\n\u003cp>Gilad Doitsh spent seven years doing the research in Greene’s lab and confirming his results before he was confident enough to present his findings for publication. Today, he advises three doctoral students who are beginning to investigate the behavior of HIV, much like he did nearly a decade ago. \u003c/p>\n\u003cp>“I tell them we are like detectives,” said Doitsh. “We have a suspect – HIV. We’re sure he committed murder but we have to collect the best evidence to convince the jury so that this guy can go to jail.” \u003c/p>\n\u003cp>“You have to know every aspect of HIV. You take baby steps but if every step is solid, then you have enough proof to convict the suspect,” he added. \u003c/p>\n\u003cp>\u003c/p>\u003c/div>","attributes":{"named":{},"numeric":[]}},{"type":"component","content":"","name":"ad","attributes":{"named":{"label":"floatright"},"numeric":["floatright"]}},{"type":"contentString","content":"\u003cdiv class=\"post-body\">\u003cp>\u003c/p>\n\u003cp> 37.767050 -122.391139\u003c/p>\n\n\u003c/div>\u003c/p>","attributes":{"named":{},"numeric":[]}}],"link":"/quest/10853/aids-researchers-unlock-cell-death-mystery","authors":["6176"],"categories":["quest_4","quest_12"],"tags":["quest_89","quest_520","quest_1212","quest_1217","quest_1218","quest_1375","quest_1927","quest_13203","quest_3026","quest_3102"],"featImg":"quest_11177","label":"quest"}},"programsReducer":{"possible":{"id":"possible","title":"Possible","info":"Possible is hosted by entrepreneur Reid Hoffman and writer Aria Finger. Together in Possible, Hoffman and Finger lead enlightening discussions about building a brighter collective future. The show features interviews with visionary guests like Trevor Noah, Sam Altman and Janette Sadik-Khan. Possible paints an optimistic portrait of the world we can create through science, policy, business, art and our shared humanity. It asks: What if everything goes right for once? How can we get there? Each episode also includes a short fiction story generated by advanced AI GPT-4, serving as a thought-provoking springboard to speculate how humanity could leverage technology for good.","airtime":"SUN 2pm","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Possible-Podcast-Tile-360x360-1.jpg","officialWebsiteLink":"https://www.possible.fm/","meta":{"site":"news","source":"Possible"},"link":"/radio/program/possible","subscribe":{"apple":"https://podcasts.apple.com/us/podcast/possible/id1677184070","spotify":"https://open.spotify.com/show/730YpdUSNlMyPQwNnyjp4k"}},"1a":{"id":"1a","title":"1A","info":"1A is home to the national conversation. 1A brings on great guests and frames the best debate in ways that make you think, share and engage.","airtime":"MON-THU 11pm-12am","imageSrc":"https://ww2.kqed.org/radio/wp-content/uploads/sites/50/2018/04/1a.jpg","officialWebsiteLink":"https://the1a.org/","meta":{"site":"news","source":"npr"},"link":"/radio/program/1a","subscribe":{"npr":"https://rpb3r.app.goo.gl/RBrW","apple":"https://itunes.apple.com/WebObjects/MZStore.woa/wa/viewPodcast?s=143441&mt=2&id=1188724250&at=11l79Y&ct=nprdirectory","tuneIn":"https://tunein.com/radio/1A-p947376/","rss":"https://feeds.npr.org/510316/podcast.xml"}},"all-things-considered":{"id":"all-things-considered","title":"All Things Considered","info":"Every weekday, \u003cem>All Things Considered\u003c/em> hosts Robert Siegel, Audie Cornish, Ari Shapiro, and Kelly McEvers present the program's trademark mix of news, interviews, commentaries, reviews, and offbeat features. Michel Martin hosts on the weekends.","airtime":"MON-FRI 1pm-2pm, 4:30pm-6:30pm\u003cbr />SAT-SUN 5pm-6pm","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/All-Things-Considered-Podcast-Tile-360x360-1.jpg","officialWebsiteLink":"https://www.npr.org/programs/all-things-considered/","meta":{"site":"news","source":"npr"},"link":"/radio/program/all-things-considered"},"american-suburb-podcast":{"id":"american-suburb-podcast","title":"American Suburb: The Podcast","tagline":"The flip side of gentrification, told through one town","info":"Gentrification is changing cities across America, forcing people from neighborhoods they have long called home. Call them the displaced. Now those priced out of the Bay Area are looking for a better life in an unlikely place. American Suburb follows this migration to one California town along the Delta, 45 miles from San Francisco. But is this once sleepy suburb ready for them?","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/American-Suburb-Podcast-Tile-703x703-1.jpg","officialWebsiteLink":"/news/series/american-suburb-podcast","meta":{"site":"news","source":"kqed","order":"13"},"link":"/news/series/american-suburb-podcast/","subscribe":{"npr":"https://rpb3r.app.goo.gl/RBrW","apple":"https://itunes.apple.com/WebObjects/MZStore.woa/wa/viewPodcast?mt=2&id=1287748328","tuneIn":"https://tunein.com/radio/American-Suburb-p1086805/","rss":"https://ww2.kqed.org/news/series/american-suburb-podcast/feed/podcast","google":"https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy5tZWdhcGhvbmUuZm0vS1FJTkMzMDExODgxNjA5"}},"baycurious":{"id":"baycurious","title":"Bay Curious","tagline":"Exploring the Bay Area, one question at a time","info":"KQED’s new podcast, Bay Curious, gets to the bottom of the mysteries — both profound and peculiar — that give the Bay Area its unique identity. And we’ll do it with your help! You ask the questions. You decide what Bay Curious investigates. And you join us on the journey to find the answers.","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Bay-Curious-Podcast-Tile-703x703-1.jpg","imageAlt":"\"KQED Bay Curious","officialWebsiteLink":"/news/series/baycurious","meta":{"site":"news","source":"kqed","order":"4"},"link":"/podcasts/baycurious","subscribe":{"apple":"https://podcasts.apple.com/us/podcast/bay-curious/id1172473406","npr":"https://www.npr.org/podcasts/500557090/bay-curious","rss":"https://ww2.kqed.org/news/category/bay-curious-podcast/feed/podcast","google":"https://podcasts.google.com/feed/aHR0cHM6Ly93dzIua3FlZC5vcmcvbmV3cy9jYXRlZ29yeS9iYXktY3VyaW91cy1wb2RjYXN0L2ZlZWQvcG9kY2FzdA","stitcher":"https://www.stitcher.com/podcast/kqed/bay-curious","spotify":"https://open.spotify.com/show/6O76IdmhixfijmhTZLIJ8k"}},"bbc-world-service":{"id":"bbc-world-service","title":"BBC World Service","info":"The day's top stories from BBC News compiled twice daily in the week, once at weekends.","airtime":"MON-FRI 9pm-10pm, TUE-FRI 1am-2am","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/BBC-World-Service-Podcast-Tile-360x360-1.jpg","officialWebsiteLink":"https://www.bbc.co.uk/sounds/play/live:bbc_world_service","meta":{"site":"news","source":"BBC World Service"},"link":"/radio/program/bbc-world-service","subscribe":{"apple":"https://itunes.apple.com/us/podcast/global-news-podcast/id135067274?mt=2","tuneIn":"https://tunein.com/radio/BBC-World-Service-p455581/","rss":"https://podcasts.files.bbci.co.uk/p02nq0gn.rss"}},"code-switch-life-kit":{"id":"code-switch-life-kit","title":"Code Switch / Life Kit","info":"\u003cem>Code Switch\u003c/em>, which listeners will hear in the first part of the hour, has fearless and much-needed conversations about race. Hosted by journalists of color, the show tackles the subject of race head-on, exploring how it impacts every part of society — from politics and pop culture to history, sports and more.\u003cbr />\u003cbr />\u003cem>Life Kit\u003c/em>, which will be in the second part of the hour, guides you through spaces and feelings no one prepares you for — from finances to mental health, from workplace microaggressions to imposter syndrome, from relationships to parenting. The show features experts with real world experience and shares their knowledge. Because everyone needs a little help being human.\u003cbr />\u003cbr />\u003ca href=\"https://www.npr.org/podcasts/510312/codeswitch\">\u003cem>Code Switch\u003c/em> offical site and podcast\u003c/a>\u003cbr />\u003ca href=\"https://www.npr.org/lifekit\">\u003cem>Life Kit\u003c/em> offical site and podcast\u003c/a>\u003cbr />","airtime":"SUN 9pm-10pm","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Code-Switch-Life-Kit-Podcast-Tile-360x360-1.jpg","meta":{"site":"radio","source":"npr"},"link":"/radio/program/code-switch-life-kit","subscribe":{"apple":"https://podcasts.apple.com/podcast/1112190608?mt=2&at=11l79Y&ct=nprdirectory","google":"https://podcasts.google.com/feed/aHR0cHM6Ly93d3cubnByLm9yZy9yc3MvcG9kY2FzdC5waHA_aWQ9NTEwMzEy","spotify":"https://open.spotify.com/show/3bExJ9JQpkwNhoHvaIIuyV","rss":"https://feeds.npr.org/510312/podcast.xml"}},"commonwealth-club":{"id":"commonwealth-club","title":"Commonwealth Club of California Podcast","info":"The Commonwealth Club of California is the nation's oldest and largest public affairs forum. As a non-partisan forum, The Club brings to the public airwaves diverse viewpoints on important topics. The Club's weekly radio broadcast - the oldest in the U.S., dating back to 1924 - is carried across the nation on public radio stations and is now podcasting. Our website archive features audio of our recent programs, as well as selected speeches from our long and distinguished history. This podcast feed is usually updated twice a week and is always un-edited.","airtime":"THU 10pm, FRI 1am","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Commonwealth-Club-Podcast-Tile-360x360-1.jpg","officialWebsiteLink":"https://www.commonwealthclub.org/podcasts","meta":{"site":"news","source":"Commonwealth Club of California"},"link":"/radio/program/commonwealth-club","subscribe":{"apple":"https://itunes.apple.com/us/podcast/commonwealth-club-of-california-podcast/id976334034?mt=2","google":"https://podcasts.google.com/feed/aHR0cDovL3d3dy5jb21tb253ZWFsdGhjbHViLm9yZy9hdWRpby9wb2RjYXN0L3dlZWtseS54bWw","tuneIn":"https://tunein.com/radio/Commonwealth-Club-of-California-p1060/"}},"considerthis":{"id":"considerthis","title":"Consider This","tagline":"Make sense of the day","info":"Make sense of the day. Every weekday afternoon, Consider This helps you consider the major stories of the day in less than 15 minutes, featuring the reporting and storytelling resources of NPR. Plus, KQED’s Bianca Taylor brings you the local KQED news you need to know.","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Consider-This-Podcast-Tile-703x703-1.jpg","imageAlt":"Consider This from NPR and KQED","officialWebsiteLink":"/podcasts/considerthis","meta":{"site":"news","source":"kqed","order":"7"},"link":"/podcasts/considerthis","subscribe":{"apple":"https://podcasts.apple.com/podcast/id1503226625?mt=2&at=11l79Y&ct=nprdirectory","npr":"https://rpb3r.app.goo.gl/coronavirusdaily","google":"https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy5ucHIub3JnLzUxMDM1NS9wb2RjYXN0LnhtbA","spotify":"https://open.spotify.com/show/3Z6JdCS2d0eFEpXHKI6WqH"}},"forum":{"id":"forum","title":"Forum","tagline":"The conversation starts here","info":"KQED’s live call-in program discussing local, state, national and international issues, as well as in-depth interviews.","airtime":"MON-FRI 9am-11am, 10pm-11pm","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Forum-Podcast-Tile-703x703-1.jpg","imageAlt":"KQED Forum with Mina Kim and Alexis Madrigal","officialWebsiteLink":"/forum","meta":{"site":"news","source":"kqed","order":"8"},"link":"/forum","subscribe":{"apple":"https://podcasts.apple.com/us/podcast/kqeds-forum/id73329719","google":"https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy5tZWdhcGhvbmUuZm0vS1FJTkM5NTU3MzgxNjMz","npr":"https://www.npr.org/podcasts/432307980/forum","stitcher":"https://www.stitcher.com/podcast/kqedfm-kqeds-forum-podcast","rss":"https://feeds.megaphone.fm/KQINC9557381633"}},"freakonomics-radio":{"id":"freakonomics-radio","title":"Freakonomics Radio","info":"Freakonomics Radio is a one-hour award-winning podcast and public-radio project hosted by Stephen Dubner, with co-author Steve Levitt as a regular guest. It is produced in partnership with WNYC.","imageSrc":"https://ww2.kqed.org/news/wp-content/uploads/sites/10/2018/05/freakonomicsRadio.png","officialWebsiteLink":"http://freakonomics.com/","airtime":"SUN 1am-2am, SAT 3pm-4pm","meta":{"site":"radio","source":"WNYC"},"link":"/radio/program/freakonomics-radio","subscribe":{"npr":"https://rpb3r.app.goo.gl/4s8b","apple":"https://itunes.apple.com/us/podcast/freakonomics-radio/id354668519","tuneIn":"https://tunein.com/podcasts/WNYC-Podcasts/Freakonomics-Radio-p272293/","rss":"https://feeds.feedburner.com/freakonomicsradio"}},"fresh-air":{"id":"fresh-air","title":"Fresh Air","info":"Hosted by Terry Gross, \u003cem>Fresh Air from WHYY\u003c/em> is the Peabody Award-winning weekday magazine of contemporary arts and issues. One of public radio's most popular programs, Fresh Air features intimate conversations with today's biggest luminaries.","airtime":"MON-FRI 7pm-8pm","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Fresh-Air-Podcast-Tile-360x360-1.jpg","officialWebsiteLink":"https://www.npr.org/programs/fresh-air/","meta":{"site":"radio","source":"npr"},"link":"/radio/program/fresh-air","subscribe":{"npr":"https://rpb3r.app.goo.gl/4s8b","apple":"https://itunes.apple.com/WebObjects/MZStore.woa/wa/viewPodcast?s=143441&mt=2&id=214089682&at=11l79Y&ct=nprdirectory","tuneIn":"https://tunein.com/radio/Fresh-Air-p17/","rss":"https://feeds.npr.org/381444908/podcast.xml"}},"here-and-now":{"id":"here-and-now","title":"Here & Now","info":"A live production of NPR and WBUR Boston, in collaboration with stations across the country, Here & Now reflects the fluid world of news as it's happening in the middle of the day, with timely, in-depth news, interviews and conversation. 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