Researchers Identify 273 Human Proteins That Play Role In HIV

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Researchers at Harvard Medical School have identified 273 human proteins that HIV uses to infect cells andreproduce, according to a study published Thursday in Science magazine,the New York Times reports. According to the Times, thestudy's findings could lead to the development of new HIV/AIDS therapies (McNeil, New York Times, 1/11).

For the study, Stephen Elledge, a Harvard geneticist, and colleagues used arelatively new technique called a "genome-wide scan," according tothe Washington Post. The researchers scanned the 21,000human genes that encode proteins and blocked each one individually to seewhether the blocked protein affected HIV's ability to infect a cell. Of the 273proteins identified, 36 -- including the CD4+ T cell and CCR5 receptors thatHIV uses to attach to a cell's surface -- previously had been identified andlinked to HIV. According to the Post, although it is likely that not allof the 273 proteins are necessary for HIV transmission and progression, most ofthem appear to be.

According to the study, the researchers found a group of proteins involved inallowing HIV to enter cells, as well as proteins involved in helping HIV'sgenetic material -- called RNA -- attach to a cell structure that then makescopies of the virus. In addition, the researchers identified proteins that helpHIV enter a cell's nucleus, as well as proteins involved in a process calledglycosylation, in which sugar molecules attach to the virus' outer surface.Without the glycosylation, HIV cannot infect human cells (Brown, WashingtonPost, 1/11). Additional research is necessary to determine what role eachof the proteins play in the progression of HIV, the AP/Chicago Tribune reports (AP/Chicago Tribune, 1/10).

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The study "provides a very important class of leads for thesynthesis" of new drugs to treat HIV/AIDS, according to David Baltimore, abiologist and HIV researcher at the CaliforniaInstitute of Technology who was not involved with the study (Lauerman, Bloomberg, 1/10). According to the Post, someavailable antiretroviral drugs -- including a newer class of medications firstapproved in 2003 and called "entry inhibitors" -- already block someof the proteins identified in the study. However, the study also identifiedproteins that have "been off the pharmaceutical radar screen," the Postreports (Washington Post, 1/11).

According to the Times, if drugs are developed to block the proteins,HIV likely will not be able to mutate in a host. However, blocking the proteinsin humans could be risky (New York Times, 1/11). The researchers saidthey "anticipate" that it is unlikely HIV could develop resistance todrugs that target the proteins because the virus "would have to evolve anew capability, not simply mutate a drug-binding site" (Reuters Health, 1/10). The study was funded by NIH, the Howard Hughes Medical Institute and the Crohn's andColitis Foundation of America (Bloomberg, 1/10).

Reaction

According to the Post, thestudy "instantly" provides scientists with "dozens of newstrategies for blocking or aborting HIV infection." Robert Gallo -- directorof the Institute of Human Virology at the University of Marylandand co-discover of HIV who was not involved with the study -- said it is"likely destined to be one of the best papers on HIV for this comingdecade." Anthony Fauci, director of NIH's National Institute of Allergy and InfectiousDiseases, said thestudy "puts on the table many, many more processes that up to this pointwere unrecognized" (Washington Post, 1/11).

However, Fauci added that it "remains to be seen if any of theseproteins" are "useful clinically." He added that the study is"hypothesis-generating, not hypothesis-solving. It creates a lot of work-- someone has to go down each of these pathways" (New York Times,1/11). Elledge said he hopes the study "leads to an acceleration ofresearch for cures for AIDS," adding, "It seems like people arestarting to forget about AIDS. It is still an incredibly important human healthproblem" (Washington Post, 1/11).

Reprintedwith permission from kaisernetwork.org. You can view the entire Kaiser Daily HIV/AIDS Report, search the archives, and sign upfor email delivery at kaisernetwork.org/email . The Kaiser Daily HIV/AIDS Reportis published for kaisernetwork.org, a free service of The Henry J. KaiserFamily Foundation.

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