{"id":6582,"date":"2002-07-11T18:30:50","date_gmt":"2002-07-11T17:30:50","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=6582"},"modified":"2014-06-05T11:15:29","modified_gmt":"2014-06-05T11:15:29","slug":"hiv-selectively-suppresses-anti-hiv-defence-cells","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/6582","title":{"rendered":"HIV selectively suppresses anti-HIV defence cells"},"content":{"rendered":"

A new study confirms what HIV researchers until now only suspected: HIV selectively disables the immune system\u2019s response against the virus by disproportionately infecting the very cells designed to fight it. In fact, CD4+ T cells programmed to fight HIV are two to five times more likely to be infected with HIV than CD4+ T cells programmed to take on other pathogens.<\/strong><\/p>\n

\u201cThis finding not only helps us better understand how the virus causes disease, it should also aid in developing effective HIV vaccines,\u201d comments Anthony S Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID). The study, conducted by scientists at NIAID\u2019s Vaccine Research Centre (VRC) and their colleagues, appears in the May 2 issue of Nature.<\/p>\n

CD4+ T cells, also called \u201chelper\u201d T cells, are HIV\u2019s primary target. These cells help direct the immune system\u2019s response to various pathogens. HIV undermines the body\u2019s ability to protect against disease by depleting these cells.<\/p>\n

From 12 HIV-positive individuals, the researchers isolated three subgroups of helper T cells: HIV-fighting cells, cytomegalovirus-fighting cells, and a \u201cmixed\u201d group. The scientists then examined these cells for evidence of HIV infection. In each case, HIV infected a much greater percentage of HIV-specific cells than cells in the other two groups. The cytomegalovirus-specific and mixed group showed no significant differences in HIV infection rates.<\/p>\n

\u201cFor years we have known that the immune system does not produce a good CD4+ T cell response against HIV, and we have postulated that this might be because HIV preferentially infects HIV-specific CD4+ cells,\u201d says Richard Koup, MD, senior study author and a senior investigator at the VRC. \u201cThis study is the first to show that this phenomenon actually happens in the body.\u201d Dr Koup and his team tested two possible mechanisms underlying this phenomenon and found evidence for both.<\/p>\n

The first occurs when the immune system initially confronts HIV. At this stage, HIV-specific CD4+ T cells are immature, or \u201cna\u00efve.\u201d These young helper cells rapidly multiply into a mature HIV-fighting army, but they are exceptionally vulnerable to viral infection during this process. So the seeds of this HIV-fighting army of helper T cells might be infected from the start, Dr Koup says, ensuring a perpetual high rate of infection among this group.<\/p>\n

The researchers found laboratory evidence for this scenario. They exposed both na\u00efve and mature helper cells to HIV, then stimulated the na\u00efve cells to multiply through several rounds of cell division. The na\u00efve cells in their transitional state were infected at a much higher rate than the mature cells, Dr Koup notes.<\/p>\n

However, HIV infects mature as well as na\u00efve helper T cells. Another explanation for the high rates of infection among CD4+ T cells might be that the mature ones rush to the front lines of the body\u2019s battle against HIV and are therefore exposed to more of the virus than are cells that fight other pathogens.<\/p>\n

To test this hypothesis, the researchers examined the cells of four HIV-positive individuals undergoing structured treatment interruption of their antiretroviral therapy. Because these individuals were past the early stage of infection, all their na\u00efve helper T cells had matured. When these patients went off antiretroviral drugs, their viral loads increased significantly, and their HIV-specific helper T cells tried to fight off the virus. Analysis showed that these cells became infected with HIV at a significantly higher rate than other helper T cells.<\/p>\n

\u201cThis experiment shows that HIV continuously and preferentially infects mature HIV-specific helper T cells as they try to fight off the virus,\u201d says Dr Koup. \u201cIn one patient, over half of all his infected CD4+ T cells were HIV-specific.\u201d<\/p>\n

This finding means that clinicians should consider the possible negative consequences of structured therapy interruptions that allow virus levels to rebound, says lead study author Daniel Douek, MD, PhD, chief of the VRC\u2019s Human Immunology Section. \u201cAlthough short courses of structured intermittent therapy do not result in increased levels of HIV,\u201d he says, \u201clonger regimens that permit the viral load to increase may result in long-term damage of the immune system\u2019s ability to fight off HIV.\u201d<\/p>\n

The study also suggests ways to design a more effective HIV vaccine, Dr Douek adds. Such a vaccine must induce a strong T-cell response against HIV. But because HIV-specific CD4+ T cells are especially vulnerable to HIV, an ideal vaccine should also create a broad and powerful CD8+ T cell response and antibodies against HIV, Douek explains. HIV does not infect CD8+ T cells, also known as cytotoxic or \u201ckiller\u201d cells.<\/p>\n

\u201cA robust CD8+ response should be an important part of an HIV vaccine, and this is the strategy we pursue at the Vaccine Research Center,\u201d Dr Douek says. \u201cWe are working on DNA \u2018prime-boost\u2019 vaccines. These two-part vaccines first prime the immune system with a shot of HIV DNA, then boost the immune response with a harmless viral vector that contains additional HIV genes. The boost enhances the CD8+ response.\u201d<\/p>\n

Comment<\/h3>\n

Scientists who study the immune systems of HIV patients have confirmed a long-standing suspicion: HIV targets the very cells programmed to attack it. The findings could help in the design of effective HIV vaccines, and also raise a caution about \u201cdrug holidays,\u201d in which HIV patients are temporarily taken off intensive drug therapy in the hopes of boosting their natural immune response to the virus. When the scientists studied four HIV patients who were temporarily taken off drug therapy as part of a clinical trial, they found that their HIV levels rose significantly. That spurred a corresponding surge in HIV-specific CD4 cells, which, in turn, gave the virus more potential targets.<\/strong><\/p>\n

\u201cThis is a sobering paper because it tells us that we have a difficult task ahead if we\u2019re going to overcome this virus,\u201d said Dr Anthony Fauci, chief of infectious diseases for the National Institutes of Health (NIH). <\/strong><\/p>\n

The findings, appearing in the journal Nature (2002;417:95-98), could have implications for efforts to produce an HIV vaccine, said the study\u2019s lead investigator, Daniel Douek of the NIH\u2019s National Institute of Allergy and Infectious Diseases. That\u2019s because the same infection-fighting cells that a vaccine would send into action in the face of HIV – the HIV-specific CD4 cells – would only provide the virus with the most attractive targets to infect. Douek said the findings suggest that a more effective vaccine would elicit a strong response of both the HIV-specific CD4 cells and the body\u2019s CD8 white blood cells – killer cells not infected by HIV – while also rallying anti-HIV antibodies.<\/strong><\/p>\n

Commentary from the CDC HIV\/STD\/TB Prevention News Update<\/p>\n

Reference:<\/p>\n

Douek DC, Brenchley JM, Betts MR et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 2002 May 2;417(6884):95-8
\nhttp:\/\/www.ncbi.nlm.nih.gov:80\/entrez\/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11986671&dopt=Abstract<\/a><\/p>\n

Source: NIAID News Release<\/p>\n","protected":false},"excerpt":{"rendered":"

A new study confirms what HIV researchers until now only suspected: HIV selectively disables the immune system\u2019s response against the virus by disproportionately infecting the very cells designed to fight it. In fact, CD4+ T cells programmed to fight HIV …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[15],"tags":[],"class_list":["post-6582","post","type-post","status-publish","format-standard","hentry","category-basic-science-and-immunology"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/6582","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=6582"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/6582\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=6582"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=6582"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=6582"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}