Researchers Identify Protein in Monkey Cells That Blocks HIV; Could Help Scientists Develop Drugs, Vaccine

Researchers have identified in monkey cells a protein that naturally blocks HIV that could help scientists develop drug treatments for HIV-positive people, according to a study published in the Feb. 26 issue of the journal Nature, the San Francisco Chronicle reports. The protein, called TRIM5-alpha, is similar to a protein found in human cells, according to the Chronicle (Russell, San Francisco Chronicle, 2/26). Researchers from the Harvard University Dana-Farber Cancer Institute and Harvard Medical School created a library of the 40,000 genes in a rhesus macaque monkey's genome and then inserted each gene into human cells that usually would be vulnerable to HIV infection, according to the Wall Street Journal (Chase, Wall Street Journal, 2/26). Researchers developed a hybrid virus using parts of HIV and the simian immunodeficiency virus that could effectively infect monkeys, the New York Times reports. The hybrid virus consisted of HIV's genetic material contained within the capsid, or protective coating, of SIV (Kolata, New York Times, 2/26). Researchers next introduced the hybrid into the cells. The hybrid virus was equipped to "emit a green florescent light" when infection occurred, the Journal reports. Cells that became infected "shone bright green" and cells in which no infection occurred remained dark, according to the Journal (Wall Street Journal, 2/26). Researchers found that TRIM5-alpha is effective at preventing HIV infection by preventing the virus from shedding its capsid, which is the first step in HIV replication after the virus has entered a cell (BBC News, 2/25). Lead researcher Joseph Sodroski said, "Cells carrying the gene for TRIM5-alpha didn't get infected, no matter how much HIV you put on them," adding, "It is really potent in blocking HIV" (Wall Street Journal, 2/26).

Human Implications
Humans carry 37 types of TRIM proteins, including TRIM5-alpha, the Chronicle reports. Researchers have yet to identify the function for most of the proteins, but the proteins appear to be "naturally evolved" to fight viruses that contain RNA, the main genetic component of HIV, according to the Chronicle (San Francisco Chronicle, 2/26). Previous studies have shown that the human version of TRIM5-alpha is 87% identical to the monkey version of the protein, and further research will be needed to examine why the monkey version blocks HIV but the human version does not. Sodroski said, "If we can just potentiate the protein to make up the difference, it might be possible to block transmission or treat infected people" (Tasker, Miami Herald, 2/26). He added, "We're still trying to understand exactly how it works." In an accompanying commentary, Columbia University molecular biologist Stephen Goff said that after the mechanisms of TRIM5-alpha are known, "the next goal will be to recreate its effects in a therapeutic treatment" (San Francisco Chronicle, 2/26). Sodroski said, "We expect that now that we've identified this protein factor, it is likely we'll find ways to manipulate it and increase its potency and we hope to stimulate our own natural resistance to HIV by doing so" (AP/Washington Times, 2/26).

Reaction
Keith Alcorn, editor of the Web site aidsmap.com, said, "There are two possible avenues for developing a treatment based on this discovery. One is to boost the human body's own production of this protein, the other is to make a copy that can be given as a medicine" (BBC News, 2/25). National Institute of Allergy and Infectious Diseases Director Anthony Fauci said, "Identification of this HIV-blocking factor opens new avenues for intervening in the early stage of HIV infection, before the virus can gain a toehold. Basic discoveries like this provide the scientific springboard to future improvements in therapies for HIV disease" (Reaney, Reuters, 2/25). Carl Dieffenbach, director of basic science research for AIDS at NIH, said, "This will go immediately in about 15 different directions," adding, "This has been an amazing year in basic research and now we've got this. We're very rich with results, and we've got a lot to work on" (Miami Herald, 2/26). The research was funded by grants from NIAID, the International AIDS Vaccine Initiative, the Bristol-Myers Squibb Foundation and the Center for AIDS Research of the Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center and Children's Hospital Boston (Wall Street Journal, 2/26).