Researchers Identify 273 Human Proteins That Play A Role In HIV Transmission, Progression

Main Category: HIV / AIDS
Also Included In: Genetics
Article Date: 14 Jan 2008 - 8:00 PDT

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Researchers at Harvard Medical School have identified 273 human proteins that HIV uses to infect cells and reproduce, according to a study published Thursday in Science magazine, the New York Times reports. According to the Times, the study'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 a relatively new technique called a "genome-wide scan," according to the Washington Post. The researchers scanned the 21,000 human genes that encode proteins and blocked each one individually to see whether the blocked protein affected HIV's ability to infect a cell. Of the 273 proteins identified, 36 -- including the CD4+ T cell and CCR5 receptors that HIV uses to attach to a cell's surface -- previously had been identified and linked to HIV. According to the Post, although it is likely that not all of the 273 proteins are necessary for HIV transmission and progression, most of them appear to be.

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

The study "provides a very important class of leads for the synthesis" of new drugs to treat HIV/AIDS, according to David Baltimore, a biologist and HIV researcher at the California Institute of Technology who was not involved with the study (Lauerman, Bloomberg, 1/10). According to the Post, some available antiretroviral drugs -- including a newer class of medications first approved in 2003 and called "entry inhibitors" -- already block some of the proteins identified in the study. However, the study also identified proteins that have "been off the pharmaceutical radar screen," the Post reports (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 proteins in humans could be risky (New York Times, 1/11). The researchers said they "anticipate" that it is unlikely HIV could develop resistance to drugs that target the proteins because the virus "would have to evolve a new 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 and Colitis Foundation of America (Bloomberg, 1/10).

Reaction
According to the Post, the study "instantly" provides scientists with "dozens of new strategies for blocking or aborting HIV infection." Robert Gallo -- director of the Institute of Human Virology at the University of Maryland and 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 coming decade." Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said the study "puts on the table many, many more processes that up to this point were unrecognized" (Washington Post, 1/11).

However, Fauci added that it "remains to be seen if any of these proteins" 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 of research for cures for AIDS," adding, "It seems like people are starting to forget about AIDS. It is still an incredibly important human health problem" (Washington Post, 1/11).

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