Why Some HIV Carriers Never Develop AIDS

choi

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Stephen Smith, Gene research finds clues to AIDS survival; Boston-led study is part of vaccine search. Boston Globe, Nov. 5, 2010.
http://www.boston.com/news/local/massachusetts/articles/2010/11/05/gene_research_finds_clues_to_aids_survival/
("The genetic testing found something distinctive about that warning system in controllers — differences in five amino acids, which are the building blocks of proteins. In those people, a tiny groove in a molecule that is part of the warning system has a particular shape, affecting how the warning flag sits atop cells")

My comment:
(a) Bruce D. Walker, MD is head of Ragon Institute.
(b) Ragon Institute of MGH, MIT and Harvard
http://www.ragoninstitute.org/about_history.html
(at Massachusetts General Hospital - East, Charlestown, Massachusetts; establishment announced on Feb. 4, 2009; founded through a $100 million gift – the largest gift in MGH history – from the Phillip T. and Susan M. Ragon Institute Foundation)
(c) Broad Institute of MIT and Harvard
http://www.broadinstitute.org/
(at three far-flung buildings at City of Cambridge, Mass.; founded in 2003 and launched in 2004 through the extraordinary generosity and remarkable vision of Los Angeles-based philanthropists Eli and Edythe Broad; head Eric Lander)
(d) The report refers to

The International HIV Controllers Study, The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation. Science, __: __ (published online Nov. 4, 2010)
http://www.sciencemag.org/cgi/content/abstract/sci;science.1195271v1?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=hiv&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

(i) I just clicked "FULL TEXT (PDF)" in the upper left corner of this page, and browse through it. The Science article identifies five amino acid mutation in HLA-B that can protect HIV carriers (called "controllers" in the Globe report).

"The results of this procedure provided evidence that multiple amino acid
positions in the peptide binding groove are indeed associated with host control (table S7), including 62, 63, 67, 70, and 97, thus providing a structural basis for the effect of HLA-B on host control (Fig. 4)." web page 3 (page number is at the bottom of each web page).

* For Figure 4, go to the very last, whose caption is at web page 4.

(ii) Naturally each controller has one mutation, not all five at the same time. apparently one mutation at the five critical points is enough to protect a controller. As for how (whether the mutation foils or facilitates presentation of a peptide), the (Science) article does not say--it is for another day.
(iii) If you are a layperson (as opposed to a trained biologist), you will not be able to read the Science article. The Globe report is easy enough for ordinary people.



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