ÿþ<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd"> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title>Human Immunodeficiency Virus 1 (HIV-1): host defense and patients' categories at MetaPathogen </title> <meta name="description" content="Human Immunodeficiency Virus 1: host defense and patients' categories at MetaPathogen" /> <meta name="keywords" content="Human Immunodeficiency Virus 1,HIV,HIV-1,HIV-2,SIV,AIDS,Cell-Mediated Adaptive Immunity,humoral immunity,CD4,CD38,chemokines,Classical LTNP,elite controller,long-term non-progressors,Human leukocyte antigen" /> <link rel="Stylesheet" href="../cannotfind.css" /> <link rel="stylesheet" href="../organisms.css" type="text/css" /> </head> <!-- TRACKIN CODE--> <script type="text/javascript"> var _gaq = _gaq || []; _gaq.push(['_setAccount', 'UA-21363345-12']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); </script> <!--TRACKING CODE--> <body> <h1 class="header"> MetaPathogen.com/Human Immunodeficiency Virus 1</h1> <h1 class="empty"> &nbsp;</h1> <div class="announce-left"> <img src="../IMG/abstract-img1.png" alt="Abstract image" /> </div> <div class="announce-right"> <img src="../IMG/abstract-img2.png" alt="Abstract image" /> </div> <div class="nav-left"> <a href="http://www.MetaPathogen.com" class="nav-mine" title="http://www.MetaPathogen.com is pathogen-oriented website">http://www.MetaPathogen.com</a><br/> <div class="google-ad-left"> <!-- ADDTHIS BUTTON --> <a class="addthis_button" href="http://addthis.com/bookmark.php?v=250&amp;pub=nemose"><img src="http://s7.addthis.com/static/btn/v2/lg-bookmark-en.gif" width="125" height="16" alt="Bookmark and Share" style="border:0"/></a><script type="text/javascript" src="http://s7.addthis.com/js/250/addthis_widget.js#pub=nemose"></script> <!--ADDTHIS BUTTON --> </div> <h4 class="link-group">Data and reports</h4> <a href="../survival/" class="nav-mine" title="Survival of selected pathogens">Pathogen survival</a><br/> <a href="../famous-artists-deaths.html" class="nav-mine" title="Famous people's cause of death">Famous people deaths</a><br/> <br /> <h4 class="link-group">Human pathogens</h4> <a href="../bacterial-pathogens/" class="nav-mine" title="List of bacterial human pathogens">Bacterial pathogens</a><br/> <a href="../fungal-pathogens/" class="nav-mine" title="List of bungal human pathogens">Fungal pathogens</a><br/> <a href="../protozoan-pathogens/" class="nav-mine" title="List of protozoan human pathogens">Protozoan pathogens</a><br/> <a href="../helminths/" class="nav-mine" title="List of parasitic worms">Helminths</a><br/> <a href="../DNA-viruses/" class="nav-mine" title="List of pathogenic DNA viruses">DNA Viruses</a><br/> <a href="../ssRNA-negative-strand-viruses/" class="nav-mine" title="List of pathogenic ssRNA(-) viruses">ssRNA(-) Viruses</a><br/> <a href="../ssRNA-positive-strand-viruses/" class="nav-mine" title="List of pathogenic ssRNA(+) viruses">ssRNA(+) Viruses</a><br/> <a href="../reoviruses-retroviruses/" class="nav-mine" title="List of Reoviruses and Retroid viruses">Reo- and Retroviruses</a><br/> <br /> <br /> <h4 class="link-group"><a href="../plant-pathogens/">Plant pathogens</a></h4> <a href="../plant-pathogens/plant-bacterial-pathogens.html" class="nav-mine" title="List of plant bacterial pathogens">Bacterial pathogens</a><br/> <a href="../plant-pathogens/plant-fungal-pathogens.html" class="nav-mine" title="List of plant fungal pathogens">Fungal pathogens</a><br/> <a href="../plant-pathogens/plant-oomycetes.html" class="nav-mine" title="List of plant oomycetes">Oomycetes</a><br/> <a href="../plant-pathogens/plant-parasitic-nematodes.html" class="nav-mine" title="List of plant parasitic nematodes">Parasitic Nematodes</a><br/> <a href="../plant-pathogens/plant-ssDNA-viruses.html" class="nav-mine" title="List of plant ssDNA viruses">ssDNA Viruses</a><br/> <a href="../plant-pathogens/plant-dsRNA-viruses.html" class="nav-mine" title="List of plant dsRNA viruses">dsRNA Viruses</a><br/> <a href="../plant-pathogens/plant-ss-negative-RNA-viruses.html" class="nav-mine" title="List of plant ssRNA(-) viruses">ssRNA(-) Viruses</a><br/> <a href="../plant-pathogens/plant-ss-positive-RNA-viruses.html" class="nav-mine" title="List of plant ssRNA(+) viruses">ssRNA(+) Viruses</a><br/> <a href="../plant-pathogens/plant-retro-transcribed-viruses.html" class="nav-mine" title="List of plant retro-transcribed viruses">Retro-transcribed Viruses</a><br/> <br /> <br /> <h4 class="link-group"> HIV-1</h4> <a class="nav-mine" href="index.html">HIV-1 introduction</a><br /> <a class="nav-mine" href="index.html"><img src="../IMG/HIV-publication-trends-ss.png" alt="HIV-1 publications treands" /></a><br /> <a class="nav-mine" href="HIV-1-anatomy.html">HIV-1 anatomy</a><br /> <a class="nav-mine" href="HIV-1-anatomy.html"><img src="../IMG/HIV-anatomy-1-s.png" alt="HIV-1 anatomy" /></a><br /> <a class="nav-mine" href="HIV-origin-classification.html">HIV-1 origin &amp; classification</a><br /> <a class="nav-mine" href="HIV-origin-classification.html"><img src="../IMG/cross-species-transmission-models-s.png" alt="HIV-1 cross-species transmission models" /></a><br /> <a class="nav-mine" href="HIV-1-transmission.html">HIV-1 transmission</a><br /> <a class="nav-mine" href="HIV-1-transmission.html"><img src="../IMG/HIV-infectious-synapse.jpg" width="150" height="129" alt="HIV-1 infectious synapse model" /></a><br /> <a class="nav-mine" href="HIV-1-replication.html">HIV-1 life cycle</a><br /> <a class="nav-mine" href="HIV-1-replication.html"><img src="../IMG/HIV-entry-s.png" alt="HIV-1 entry into cell" /></a><br /> <a class="nav-mine" href="HIV-1-disease-progression.html">HIV-1 disease progression</a><br /> <a class="nav-mine" href="HIV-1-disease-progression.html"><img src="../IMG/hiv-viral-load-dynamics-2s.png" alt="HIV viral load dynamics " /></a><br /> <a class="nav-mine" href="HIV-1-treatment.html">HIV-1 treatment</a><br /> <a class="nav-mine" href="HIV-1-treatment.html"><img src="../IMG/hiv-viral-load-dynamics-s.png" alt="HIV viral load dynamics " /></a><br /> <a class="nav-mine" href="HIV-testing.html">HIV-1 testing</a><br /> <a class="nav-mine" href="HIV-testing.html"><img src="../IMG/HIV-1-markers-small.png" alt="HIV-1 markers' dynamics" /></a><br /> <a class="nav-mine" href="HIV-1-host-organism.html">HIV-1 patients &amp; host defense</a><br /> <a class="nav-mine" href="HIV-survival.html">HIV-1 survival</a><br /> <a class="nav-mine" href="HIV-resources.html">Resources and help</a><br /> <a class="nav-mine" href="HIV-bibliography.html">Bibliography</a> <div class="google-ad-left"> <!-- GOOGLE AD --> <!-- GOOGLE AD --> </div> <h4 class="link-group"> MetaPathogen</h4> <h4 class="link-group"> T-shirts &amp; </h4> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/Staphylococcus-T-shirt.bmp" alt="Staphylococcus T shirt" /> </a> <br /> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/planarian-T-shirt.jpg" alt="Planarian T shirt " /> </a> <h4 class="link-group"> accessories</h4> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/dwarf-puffer-tote-bag.bmp" alt="Dwarf puffer mug" /> </a> <br /> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/Pushkin-dog-T-shirt.bmp" alt="Pushkin dog T-shirt" /> </a><br /> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/owl-framed-tile.png" alt="Owl framed tile" /> </a> <h4 class="link-group"> jewelry</h4> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/owl-neckless-oval-charm.png" alt="Owl necklace oval charm" /> </a><br /> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/white-daffodils-charm.bmp" alt="White daffodils charm necklace" /> </a><br /> <h4 class="link-group"> science posters</h4> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/Lyme-disease-transmission-poster.bmp" alt="Lyme disease poster" /> </a><br /> <a target="_blank" href="http://www.cafepress.com/GeoChemBio" class="nav-mine" title="GeoChemBio CafePress Shop"> <img src="../IMG/cafepress/human-bacterial-pathogens.jpg" alt="Human bacterial pathogens" /> </a><br /> <div class="google-ad-left"> <p>&nbsp;</p> </div> <div class="google-ad-left"> <p>&nbsp;</p> </div> <div class="google-ad-left"> <p>&nbsp;</p> </div> <div class="google-ad-left"> <p>&nbsp;</p> </div> <div class="google-ad-left"> <p>&nbsp;</p> </div> </div> <div class="nav-right"> <!-- <a href="http://www.AntiGeneX.com" class="nav-mine" title="http://www.AntiGeneX.com is a website that specializes on anti-gene technology">http://www.AntiGeneX.com</a><br/> <a href="http://www.ArgusDream.com" class="nav-mine" title="http://www.ArgusDream.com is a dream of Argus who never slept">http://www.ArgusDream.com</a><br/> <a href="http://www.AtlasShoulders.com" class="nav-mine" title="http://www.AtlasShoulders.com is a website that supports people and environment">http://www.AtlasShoulders.com</a><br/> <a href="http://www.CannotFindLand.com" class="nav-mine" title="http://www.CannotFindLand.com is a parked domain">http://www.CannotFindLand.com</a><br/> <a href="http://www.CannotFindName.com" class="nav-mine" title="http://www.CannotFindName.com is a primary domain">http://www.CannotFindName.com</a><br/> <a href="http://www.CreativeSpasms.com" class="nav-mine" title="http://www.CreativeSpasms.com is website for creative people">http://www.CreativeSpasms.com</a><br/> <a href="http://www.CurioScope.com" class="nav-mine" title="http://www.CurioScope.com collects curious and useful information">http://www.CurioScope.com</a><br/>--> <a href="http://www.GeoChemBio.com" class="nav-mine" title="http://www.GeoChemBio.com - general biology"> http://www.GeoChemBio.com</a><br /> <!-- <a href="http://www.GoodLuckJourney.com" class="nav-mine" title="http://www.GoodLuckJourney.com is a travel-oriented website">http://www.GoodLuckJourney.com</a><br/> <a href="http://www.HermesStaff.com" class="nav-mine" title="http://www.HermesStaff.com is a multifunctional website">http://www.HermesStaff.com</a><br/> <a href="http://www.InnocentDelights.com" class="nav-mine" title="http://www.InnocentDelights.com is a website about getting pleasure innocently">http://www.InnocentDelights.com</a><br/> <a href="http://www.JollyOwl.com" class="nav-mine" title="http://www.JollyOwl.com is a imaginary brand website">http://www.JollyOwl.com</a><br/> <a href="http://www.JollyThing.com" class="nav-mine" title="http://www.JollyThing.com should be jolly website">http://www.JollyThing.com</a><br/>--> <a href="http://www.MetaMicrobe.com" class="nav-mine" title="http://www.MetaMicrobe.com is microorganisms-oriented website"> http://www.MetaMicrobe.com</a><br /> <a href="http://www.MetaPathogen.com" class="nav-mine" title="http://www.MetaPathogen.com is pathogen-oriented website"> http://www.MetaPathogen.com</a><br /> <a href="http://www.MetaPrimate.com" class="nav-mine" title="http://www.MetaPrimate.com is biology-oriented website"> http://www.MetaPrimate.com</a><br /> <!-- <a href="http://www.MetaRodent.com" class="nav-mine" title="http://www.MetaRodent.com is biology-oriented website"> http://www.MetaRodent.com</a><br /> <a href="http://www.Nemose.com" class="nav-mine" title="http://www.Nemose.com">http://www.Nemose.com</a><br/> <a href="http://www.OxenHill.com" class="nav-mine" title="http://www.OxenHill.com is generic website about people">http://www.OxenHill.com</a><br/> <a href="http://www.PerpetualBuzz.com" class="nav-mine" title="http://www.PerpetualBuzz.com is website that has several potential uses">http://www.PerpetualBuzz.com</a><br/> <a href="http://www.RipeChance.com" class="nav-mine" title="http://www.RipeChance.com is game-oriented website">http://www.RipeChance.com</a><br/>--> <a href="http://www.StopCodons.com" class="nav-mine" title="http://www.StopCodons.com is biology-oriented website"> http://www.StopCodons.com</a><br /> <!-- <a href="http://www.Surgene.com" class="nav-mine" title="http://www.Surgene.com is website that specializes on various gene manipulation techniques">http://www.Surgene.com</a><br/> --> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <!-- AFFINITYCLICK (BANNER) --> <script type="text/javascript" id="AC-ac870710-201a-012e-926d-123139099851">var _ac = (_ac||[]); _ac.push(["_id", "ac870710-201a-012e-926d-123139099851"]); (function() { if(_ac.length == 1) { var ac = document.createElement('script'); ac.src = ('https:' == document.location.protocol ? 'https://ssl-' : 'http://') + 'js.cdn.ac/ac.js'; ac.setAttribute('async', 'true'); document.documentElement.firstChild.appendChild(ac); }})();</script> <!-- /AFFINITYCLICK (BANNER)--> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <!-- GOOGLE AD --> <!-- GOOGLE AD --> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> <div class="google-ad-right"> <p>&nbsp;</p> </div> </div> <div class="content"> <div class="centered"> <!-- chitika AD--> <script type="text/javascript"> ch_client = "nemose"; ch_width = 550; ch_height = 90; ch_type = "mpu"; ch_sid = "metapathogen"; ch_backfill = 1; ch_color_site_link = "#0000CC"; ch_color_title = "#0000CC"; ch_color_border = "#FFFFFF"; ch_color_text = "#000000"; ch_color_bg = "#FFFFFF"; </script> <script src="http://scripts.chitika.net/eminimalls/amm.js" type="text/javascript"> </script> <!-- chitika AD--> </div> <p> &nbsp;</p> <h2> <a name="top">Human Immunodeficiency Virus 1<br /> (HIV-1) and host organism</a></h2> <div class="centered"> <!--Print friendly--> <script src="http://cdn.printfriendly.com/printfriendly.js" type="text/javascript"></script><a href="http://www.printfriendly.com" class="printfriendly" onclick="window.print(); return false;" title="Print an optimized version of this web page"><img style="border:none;" src="http://cdn.printfriendly.com/pf-button-both.gif" alt="Print"/></a> <!--Print friendly--> </div> <h3>Categories of people in relation to HIV-1 disease</h3> <ul class="keyword"> <li><span class="term">"Normal" HIV-1 <br />infected persons</span><span class="def"> Highly variable disease progression rates between individuals are well-recognized, with progression categorized as rapid, typical or intermediate and late or long-term non-progression. The majority of infected individuals (70 80%) experience intermediate disease progression in which they develop AIDS-related illnesses within 6 10 years of acquiring HIV. Ten to 15% are rapid progressors who have a fast CD4+ T-cell decline and occurrence of AIDS-related events within a few years after infection. The late progressors (5%), can remain healthy without significant changes in CD4 count or HIV-RNA for over 10 years. This wide variation in speed of disease progression depends on combination of immunological and virological factors, host genetics and other host factors (age, weight, psychological factors, health status).<br /> Immunological factors: T-lymphocytes' (CD4+ and CD8+) count and function and immune activation (immune-activation-driven apoptosis of CD4+ cells, more than a direct virological pathogenic effect, is responsible for the decline in CD4+). <br /> Virological factors are viral load at set point, resistance mutations, chemokine receptor tropism, and viral subtype and race. <!--not only on virus strain acquired by the patient but also, to a very high extent, on the patient's genetic makeup and initial health conditions. The acute infection is followed by a decrease in viremia that coincides with CTL induction. In the chronic infection phase, the strength of the CTL activity is inversely correlated with the viral load and the speed of disease progression. Despite vigorous HIV-1 specific <em>Cytopathic T- Lymphocyte (CTL)</em> responses in most infected individuals, viral replication persists and eventually overwhelms the immune system. Among the possible reasons of immune failure, <em>viral escape mutations</em> in CTL-targeted epitopes are considered most important. Viral escape is readily possible because the interaction of the T-cell receptor with the epitope/MHC-I complex is highly specific and even minor alterations of the epitope sequence abolish recognition. Many different HIV-1 epitopes are targeted by CTLs. The CTL specificity evolves over time from targeting proteins such as Tat and Nef in the early phase and towards the structural proteins in chronic infection.--> </span></li> <li><span class="term">Exposed <br />seronegative <br />individuals (ESN) </span> <span class="def"> ESN is someone who is not HIV-infected despite a history of multiple unprotected sexual episodes (with an HIV-seropositive partner) for 4 years or longer, with at least eight episodes of at-risk intercourse within the 4 months before study entry and an average of 30 reported unprotected sexual contacts per year. Individuals homozygous for the D32 allelic variant of the CCR5 protein, the co-receptor for the macrophago-tropic R5-HIV viruses, display a strong protection to sexually transmitted HIV infection. However, protection is not absolute and some rare cases of HIV-1 infection despite this genotype have been reported. These patients harboured CXCR4-using viruses, suggesting that CXCR4 was the co-receptor responsible for initiating infection. The CCR5 D32 allele occurs with a frequency of 4 15% in Caucasian ethnicity (even higher frequencies can be observed in Northern Europeans) and homozygous individuals are overrepresented in ESN. The CCR5 D32 variant is nevertheless completely absent in sub-Saharian African populations, where the majority of HIV infection occurs and where many investigators have described numerous cohorts of ESN. </span></li> <li><span class="term">Long-term <br />non progressors </span><span class="def">A small minority (&lt;2%) of HIV-seropositive patients characterized by a long course infection that does not result in signs or symptoms of AIDS, despite the absence of antiretroviral therapy. CD4 T cell counts are stable and HIV plasma viremia is low in LTNP. LTNPs form a very heterogeneous population. Indeed, these patients, <em>being only defined on an immunological basis</em> (CD4+ count), have highly variable viral loads, and up to 90% of individuals included in LTNP cohorts eventually had a decline in their CD4+ T cell counts and progress to AIDS. </span> <ul class="keyword"> <li><span class="term">"Classical" LTNP</span> <span class="def"> Show variable and low but detectable viral load (&lt;5000 HIV-RNA copies/ml), maintain healthy CD4+ cell counts for 20 years and more; eventually may progress to AIDS. </span></li> <li><span class="term">Elite controllers</span> <span class="def">Characterized by a consistently undetectable plasma viremia (&lt;50 copies/ml). Also called <em>HIV controllers (HICs)</em>, they are also known as <em>elite controllers</em>, <em>elite suppressors</em>, or <em>elite nonprogressors</em>. HICs appear to represent less than 1% of all HIV-infected patients. All HICs are fully HIV seropositive and have very low and stable amounts of viral DNA in their peripheral blood mononuclear cells (PBMC). <em>An effective, multifunctional HIV-specific CD8+ T-cell response is thought to be central to viral control in these individuals.</em> </span> </li> </ul> </li> </ul> <p> Lately, the International HIV Controller Consortium has somewhat relaxed the requirements that define this population of HIV-infected individuals. Thus, by the new definition, elite controllers are HIV-infected patients with HIV RNA levels below 50 copies/ml) despite the absence of antiretroviral therapy (for at least 1 year at the time of the study). Spikes of viremia up to 1000 copies/ml) are accepted in elite controllers, as long as these episodes are not consecutive and represent the minority of all available determinations.<br /> A temporary increase in VL in someone who previously had undetectable virus and who later returns to having undetectable virus is called <em>blip</em>. The viral load during a blip is usually low (50 to 500 copies/mL). </p> <p> It is actually impossible to predict whether the resistance to disease progression shown by LTNP and elite controllers will last indefinitely or whether progression to AIDS will eventually be detected in these patients. </p> <h4>Mechanisms that help to maintain undetectable plasma viral loads </h4> <ul> <li><h5>Non-cytotoxic, non-major histocompatability complex (MHC)-restricted antiviral activity</h5> This activity is mediated by soluble factors such as <em>cytidine deaminases</em> (e.g. APOBEC3G), which induce lethal hypermutations of the viral genome, <em>Fv1/TRIM5&#945;</em> proteins, which restrict the incoming retroviral capsid, and <em>tetherin</em>, which impedes the release of nascent HIV virions from the cell surface. Recent analyses have shown that these host factors all evolved under positive selective pressure due to past encounters with ancient viruses.</li> <li><h5>An HLA-class I-restricted cytotoxic T lymphocyte (CTL) response</h5> <em>Human leukocyte antigen (HLA)</em> (also known as <em>major histocompatibility complex (MHC))</em> genes are highly polymorphic loci encoding for cellular surface molecules that are responsible for antigen presentation to T lymphocytes. The efficiency of this process differs amongst individuals because of the high number of allelic variants of <em>HLA class I</em> (A, B and C) and <em>HLA class II genes</em> (DR, DQ and DP). The HLA class I genes encode molecules that bind antigens derived from the processing of intracellular pathogens and present these antigens to <em>cytotoxic T lymphocytes</em> (CTL). In contrast, HLA class II genes produce molecules that bind peptides of extracellular origin and present them to CD4+ T helper lymphocytes. Individuals expressing the most polymorphic HLA variants and those variants with the best ability to bind to exogenous peptides, mount a more vigorous immune response against pathogens. Many studies report solid, confirmed associations between HLA molecules and different patterns of HIV disease. Most notably, HLA-B*57 and HLA-B*27 have been associated with long-term survival. Both of these class I molecules restrict CTL responses by presenting peptides selected from highly conserved regions of Gag. Mutations that allow escape from these CTL-specific responses arise only at great cost to viral fitness which is translated into higher genetic diversity of viral quasispecies, lower viral loads, and greater survival benefits. However, less than 50% of elite controllers show the presence of HLA-B*57 and an even smaller percentage (20%) express HLA-B*27. </li> </ul> <h4>Characteristics of CD8+ T cells from elite controllers </h4> <ul> <li>The ability to generate a multifunctional response after stimulation with their cognate antigen that includes <em>degranulation</em> (releases antimicrobial cytotoxic molecules from secretory vesicles called granules) and chemokine and cytokine secretion (including IL-2).</li> <li>The ability to proliferate upon antigenic stimulation (progressors' lack of CD8+ T cell proliferation in response to HIV antigen stimulation reflects the impaired function of these cells).</li> </ul> <h5>Comparison of HIV-1 patients' immunological profiles</h5> <table class="regular"> <tr> <td class="regular"> progressors -HAART </td> <td class="regular"> high CD38 and HLA-DR expression (chronically activated) </td> <td class="regular"> PD-1 high (leads to apoptosis and death) </td> </tr> <tr> <td class="regular"> progressors +HAART </td> <td class="regular"> low CD38 and HLA-DR expression (not activated) </td> <td class="regular"> PD-1 low </td> </tr> <tr> <td class="regular"> elite controller </td> <td class="regular"> low CD38 (not activated) and high HLA-DR expression (a high capacity for expansion) </td> <td class="regular"> PD-1 low </td> </tr> </table> <h5>Conclusion</h5> <p> The activation phenotype of HIV-specific CD8+ T cells with their discordant phenotype in HICs is unusual. This phenotype might indicate optimal activation associated with efficient antiviral activity, whereas high CD38 expression in progressors could be due to high viral load and be driven by cytokines. This deleterious activation status can lead to PD-1 expression, inefficiency, senescence, and, ultimately, apoptosis. By contrast, PD-1 expression by HIV-specific CD8+ T cells is low in HICs. </p> <a href="#top">Back to top</a> <img src="../IMG/Nemose-ruler.png" alt="Nemose" /> <!--GOOGLE SEARCH--> <!--GOOGLE SEARCH--> <h3>Related definitions</h3> <ul class="keyword"> <li> <span class="term">Cell-Mediated<br />Adaptive<br /> Immunity</span> <span class="def">Immune protection provided by the direct action of immune cells such as CD8 cells, macrophages, and other white blood cells, rather than by antibodies.</span> </li> <li> <span class="term">Humoral Immunity</span> <span class="def">Antibody-based immune response. Immune cells called <em>B-cells</em> produce antibodies against foreign invaders.</span> </li> <li> <span class="term">Chemokines</span> <span class="def">Proteins that serve as chemical messengers to control the activities of the immune system.</span> </li> <li> <span class="term">Cytokine</span> <span class="def">A protein produced by leukocyte (white blood cell) that acts like a chemical messenger between cells. Cytokines are essential for a coordinated immune response. Cytokines include interleukines (examples: IL-2, IL-7) and interferons (INF).</span> </li> <li> <span class="term">HLA-DR</span> <span class="def">A major histocompatibility complex, MHC class II, cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31.</span> </li> <li> <span class="term">CD38 <br />(cluster of <br /> differentiation 38)</span> <span class="def"> Also known as cyclic ADP ribose hydrolase. A glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling. The CD38 protein is a marker of cell activation.</span> </li> <li> <span class="term">CD4<br /> (cluster of <br />differentiation 4)</span> <span class="def"> A glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells.</span> </li> <li> <span class="term">CD4+ cell</span> <span class="def"> Also known as <em>helper T cell</em> or <em>CD4+ lymphocyte</em>. A type of infection-fighting white blood cell that carries the CD4 receptor on its surface. By providing help to B cells and CD8+ T cells, CD4+ T cells play an important role in the humoral and cytotoxic response to pathogens. They also play a key role in down modulating immune responses thereby preventing chronic inflammation. Chronic activation of CD4+ cells as a result of HIV infection is one of the main reasons of their death. The loss of CD4+ T cells leads to the collapse of the immune response in patients with progressive disease. </span> </li> <li> <span class="term">CD8+ Cell</span> <span class="def"> Also called a <em>cytotoxic T lymphocyte (CTL)</em> or <em>killer cell</em>, or <em>suppressor cell</em>. A type of white blood cell that is able to identify and kill cells infected with bacteria, viruses, or foreign invaders.</span> </li> <li> <span class="term">Macrophage</span> <span class="def"> A relatively long-lived phagocytic cell involved in antigen presentation and other immune surveillance functions in mammalian tissues.</span> </li> <li> <span class="term">PD-1</span> <span class="def"><em>Programmed Death 1</em>, a Type I membrane protein of 268 amino acids. PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators.</span> </li> </ul> <a href="#top">Back to top</a> <img src="../IMG/Nemose-ruler.png" alt="Nemose" /> <h4> Literature</h4> <ul> <li> <p> Taborda-Vanegas N, Zapata W, Rugeles MT. <em>Genetic and Immunological Factors Involved in Natural Resistance to HIV-1 Infection.</em> <a class="external" target="_blank" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109745/" title="Review"><i>Open Virol J. 2011;5:35-43.</i></a> </p> <p class="centered"> <img src="../IMG/mechanisms-of-protection-against-HIV.jpg" alt="Mechanisms of protection against HIV-1" /> </p> <em>Mechanisms of resistance involved in the protection against HIV-1-infection and AIDS-progression. </em><br /> <ol> <li>Target cells have polymorphisms in CCR5 gene or other alternative viral coreceptors, such as CCR2 (1), all of them induce low or non-expression of these coreceptors, inhibiting viral entry.</li> <li>This step can be also blocked by high production of the coreceptors ligands, MIP-1±/², RANTES and SDF-1 (2).</li> <li>Elevated spontaneous and inducible apoptosis of monocytes and other HIV-1-target cells has been reported in ESNs (3). </li> <li>Increased release of soluble antiviral factors APOBEC3G, CAF, ± and ²- defensins, type I IFN, LIF, MIP-1±/², RANTES, RNases, SDF-1, SLPI, TRIM5± and elafin block viral entry or replication (4).</li> <li> ESNs individuals exhibit high activity in NK cells and DCs. NK cells express KIR3DS1 and KIR3DL1 related to cell activation (5) </li> <li>and are able to produce IFN-³ (6). DCs also produce IFN-± (6).</li> <li>and express the co-stimulatory molecules CD80 and CD86 (7) </li> <li> Type I IFN induces HLA expression, apoptosis of infected cells, production of antiviral molecules, and block viral replication. The specific immune response is characterized by the presence of CTLs restricted to HLA-B57 and  B27, presenting immunodominant peptides (8),</li> <li> production of cytokines such as RANTES, MIP-1², IL-6, IFN-³, TNF-± and ² and IL-2 that increase the immune response and expression of markers associated with T cell activation (9).</li> <li> B-cells produce neutralizing IgA antibodies, detectable in serum, mucosa and breast milk (10).</li> </ol> </li> <li> <p> Strebel K, Luban J, Jeang KT. <em>Human cellular restriction factors that target HIV-1 replication.</em> <a class="external" target="_blank" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759957/?tool=pubmed" title="Review"><i>BMC Med. 2009 Sep 16;7:48.</i></a> </p> <!-- <p class="centered"> <img src="../IMG/Steps-of-HIV-transmission.jpg" alt="Steps of HIV transmission" /> </p>--> <p> Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, authors discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5±), and cellular microRNAs as examples of host restriction factors that target HIV-1. </p> </li> </ul> <a href="#top">Backto top</a> <img src="../IMG/Nemose-ruler.png" alt="Nemose" /> <div class="centered"> <script type="text/javascript"> ch_client = "nemose"; ch_width = 500; ch_height = 250; ch_type = "mpu"; ch_sid = "metapathogen"; ch_color_site_link = "#0000CC"; ch_color_title = "#0000CC"; ch_color_border = "#FFFFFF"; ch_color_text = "#000000"; ch_color_bg = "#FFFFFF"; </script> <script src="http://scripts.chitika.net/eminimalls/amm.js" type="text/javascript"> </script> <!--chitika AD--> </div> <div> <!-- Kontera ContentLink(TM);--> <script type='text/javascript'> var dc_AdLinkColor = 'blue' ; var dc_PublisherID = 79943 ; </script> <script type='text/javascript' src='http://kona.kontera.com/javascript/lib/KonaLibInline.js'> </script> <!-- Kontera ContentLink(TM) --> </div> <div class="centered"> <p> &nbsp;</p> <!--SPOTBACK--> <!-- get your own widget at http://spotback.com <script src='http://spotback.com/scripts/widgets/load.js?wid=48994'></script> <noscript> <a href="http://spotback.com" alt="Rate everything widget"> <img src="http://spotback.com/images/rating.gif" alt="user rating" /></a></noscript>--> <!--SPOTBACK--> <p> &nbsp;</p> </div> <div class="centered"> <p>&nbsp;</p> <!--letsgodynamic--><!-- div56219152008 --> <script type="text/javascript" src="http://letsgodynamic.com/sm-vidm/dispatcher/call.js.php?lang=EN&clientid=SCLNT018fed78ed96a284ed5414e265e37af2"></script><div id="div56219152008"><script type="text/javascript">request_send('SVIEW5d327a1b65cdf0aa8dad077c62348d50','viewclientid=SCLNT018fed78ed96a284ed5414e265e37af2&globalid=56219152008','div56219152008','div56219152008');</script><a href="http://letsgodynamic.com">D-Modules: Comment service</a></div> <!--letsgodynamic--> <p>&nbsp;</p> </div> <div> <p class="emphasis"> Please link to this page using the code in the text area. In return, we will link to your page. Please contact us by email below. Other organisms can be found at <a class="internal" href="http://www.MetaPathogen.com" title="Pathogens and vectors"> www.MetaPathogen.com</a>, <a class="internal" href="http://www.MetaMicrobe.com" title="Various microorgamisms"> www.MetaMicrobe.com</a>, <a class="internal" href="http://www.MetaPrimate.com" title="About primates and humans"> www.MetaPrimate.com</a>, and <a class="internal" href="http://www.GeoChemBio.com" title="Animals, plants, and other organisms">www.GeoChemBio.com</a>. </p> <p class="centered"> <textarea cols="70" rows="4" name="search"><a href="http://www.MetaPathogen.com/HIV-1/HIV-1-host-organism.html" target="_blank" title="Human Immunodeficiency Virus 1 (HIV-1)">Human Immunodeficiency Virus 1 (HIV-1): host defense and patients' categories at MetaPathogen</a></textarea> </p> </div> <div class="footer"> <hr /> <p> <img src="../IMG/Nemose-black-on-white.png" alt="Nemose" /></p> <p> Last updated 08/22/11 <br/> nemose@live.com</p> <p> <a href="../privacy_policy.html" class="external" target="_blank">Privacy policy</a></p> <p> &copy;Nemose 2008 - 2012 All rights reserved</p> </div> </div> <script type="text/javascript">ggv2id='925f199a';</script> <script type="text/javascript" src="http://g2.gumgum.com/javascripts/ggv2.js"></script> </body> </html>