Natural Killer Cells Are Prominent Factors in Control of HIV
Profound Discoveries From Around the World on HIV Controllers/Long-Term Nonprogressors, Part Three
July 22, 2010
This blog entry is the third in a series of reports on a few of the scientific abstracts submitted for presentation on the subject of "HIV Controllers (HCs)" and "Long Term Nonprogressors (LTNPs) -- a small minority of HIV-positive people who control the virus in as-of-yet unexplained ways -- to the XVIII International AIDS Conference in Vienna.
I was designated an "elite controller" of HIV in 2004, when few of us were identified and information on our spontaneous and mysterious control of the virus was hard to find. I had just passed the 12th anniversary of my diagnosis by then, and was extremely curious to know what was going on -- was I going to get sick, was I going to die? My own doctor, a specialist in HIV, could not give me an explanation, and Google searches on HCs or LTNPs were not productive either, because I tried.
It's truly remarkable, then, to learn how our mysteries are being solved by researchers around the globe, and it's in this light that I share with you a few of the most intriguing abstracts (posted here in abbreviated form). I have also posted brief comments on why I believe they are important, not only to members of the HC/LTNP community, but to the entire PLWHA population.
The conference has posted full copies of all abstracts as of today, Tuesday. You may access them via this link: http://pag.aids2010.org, giving the page a bit of time to upload.
Wednesday, July 21
WEAA0104: Specific Phenotypic and Functional Features of Natural Killer Cells From HIV-Infected Long-Term Non-Progressors and HIV-Controllers
1INSERM UMR-S 945, Paris, France, 2IFR113, Paris, France
My Comments: Despite the lack of patient information involved in this cohort, I believe these findings are extremely interesting, as they contribute to the ever-expanding body of knowledge about the innate immune responses, specifically NK cells, in the HC/LTNP population. A similar study, conducted four years ago by investigators at Johns Hopkins University School of Medicine, was the first of its kind to conduct a comparison between the "magnitude of NK cell effect and CD8+ T-cell effect in elite suppressors (ES)" (another term used to describe "elite controllers"). The study team stated that NK cells were "a ... less well studied cytotoxic cell" that "may play a role in the control of HIV-1." In a cohort of 9 ES [7 women, 2 men; CD4 range 383-1125; <50 copies/mL], 7 chronic progressors [3 women, 4 men; CD4 range 200-1261; VL range 22,898-61,000 copies/mL] and 9 individuals on therapy [3 women, 6 men; CD4 range 223-1174; <50 copies/ml], the study concluded that CD8+ T-cells from ES were capable of "controlling viral replication in autologous CD4+ T-cells significantly better than CD8+ T-cells from progressors." [Source: O'Connell, et al "Role of Natural Killer Cells in a Cohort of Elite Suppressors: Low Frequency of the Protective KIR3DS1 Allele and Limited Inhibition of Human Immunodeficiency Virus Type 1 Replication In Vitro"; Journal of Virology, May 2009, p. 5028-5034, doi:10.1128/JVI.02551-08].
WEAA0105: CD4 Slope in HIV Elite and Viremic Controllers -- Data From the German NoVi Cohort
1MUC Research, Munich, Germany, 2MVZ Karlsplatz-HIV Research and Clinical Care Centre, Munich, Germany, 3HIV Outpatient Practice Kaiserdamm, Berlin, Germany, 4Private Practice for Internal Medicine, Hematology and Oncology, Mannheim, Germany, 5University Hospital of Bonn, Bonn, Germany, 6Private Practice, Berlin, Germany, 7Outpatient Practice, Stuttgart, Germany, 8Private Practice for Hematology, Oncology and Infectious Diseases, Karlsruhe, Germany, 9MVZ -- Aerzteforum Seestrasse, Berlin, Germany
My Comments: Important finding! A full 94% of HCs in this cohort retained stable CD4 counts >350 at 10 years duration of infection (although I wish the data was more clear on the results between the elite and viremic controller categories). As for the 8 individuals who experienced drops below 350 (10%), (and an increase in viral loads to >1000 copies/mL), I would have liked to see specific measurements on just how high those VLs went. This commentary would not be complete without my giving major kudos to the investigators for including such a high percentage of women -- 43% -- in this study! Hopefully this becomes a trend, instead of an exception to the rule.
WEAA04: Host Restriction and Innate Immunity to HIV Infection
WEAA0402: Analysis of TRIM5α mRNA Polymorphisms and Characterization of a Novel TRIM5α Variant Found in HIV-1 Long-Term Non-Progressors
University Medical Centre Hamburg-Eppendorf, HIV Research Laboratory, Hamburg, Germany, Heinrich-Pette-Institute, Dept. for Cell Biology and Virology, Hamburg, Germany
My Comments: Novel is good. This German team finds a novel deletion-variant, TRIM5α (δ767-867) in 30% of the LTNPs (3 of 10) that may confer a protective effect against HIV-1 infection, and state that it may represent a cellular factor that contributes to delayed progression in LTNPs. Hopefully soon, geneticists working on genome-wide association scans (GWAS) can elucidate this novel finding, and, with the current explosion of innovative approaches to immune-based and stem-cell therapies, the modification of this "mutant" TRIM5α-variant could be achieved to aid in halting progression in the general PLWHA population.
By now, dear reader, you may realize that we are witnessing one of the finest moments in the research field, as the dedicated scientists hone in on the remarkable miracle that is spontaneous control of HIV. When you consider that the killer T-cell was discovered in 1989 (thank you, Dr. Bruce Walker), you might agree that huge strides are being made in regard to our immune response to HIV infection. I'll be back tomorrow with highlights of abstracts that focus on memory B-cells, genes that confer protection against progression of disease, and, last but not least, a new discovery on how elite controllers resist, that's right, resist, HIV.
Read more of Life as an Elite Controller, Loreen Willenberg's blog, at TheBody.com.
This article was provided by TheBody. It is a part of the publication The XVIII International AIDS Conference.
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