Human Enzyme Could Hold Key to New AIDS Drug

The "latest and most exciting developmen[t]" for scientists performing basic science research on HIV is the discovery that a protein produced by HIV enables the virus to overcome the human body's natural defenses against viruses such as HIV, the San Francisco Chronicle reports. Specifically, the protein -- called Virion infectivity factor, or Vif -- inhibits the "powerful" human enzyme APOBEC3G, which in viruses similar to HIV interferes with the genetic components that the viruses use to replicate once inside a cell (Russell, San Francisco Chronicle, 7/21). Researchers Drs. Michael Malim of St. Thomas' School of Medicine at Kings College in London and Ann Sheehy of the University of Pennsylvania in July 2002 discovered that Vif suppresses CEM-15 -- an enzyme that they thought at the time was newly discovered -- allowing HIV to replicate and infect other cells. With a damaged version of Vif or a total lack of the gene that produces the protein, HIV is able to replicate. However, CEM-15 stops new HIV from exiting the cells in which they were made and thus unable to infect other cells, halting the spread of the virus within the body (Kaiser Daily HIV/AIDS Report, 7/15/02). Scientists later discovered that CEM-15 is actually the previously discovered enzyme APOBEC3G, which is thought to have evolved in mammals to fight lentiviruses -- the family of viruses of which HIV is a member.

Transforming Knowledge Into Treatment
"We now know that human beings produce a natural anti-HIV protein," Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology at the University of California-San Francisco, said, adding, "If we can somehow prevent Vif from doing its dirty work, we could unleash that protein." If scientists can discover how Vif blocks APOBEC3G, they could develop a drug that disables the protein or that prevents it from attacking the protective enzyme. Also, if scientists can gain an understanding of what makes APOBEC3G an effective virus-killer, they could perhaps produce a modified version of the enzyme that is resistant to Vif. The Vif/APOBEC3G research is part of a growing body of research into "innate immunity," the "relatively crude but effective chemical defenses" that have evolved to protect organisms against bacteria and viruses, according to the Chronicle. Many researchers have turned to examining the mechanisms involved in innate immunity because HIV seems to outwit "adaptive immunity," the body's ability to recognize invading microbes and mount a targeted immune system defense. While it is a "long, long stretch" from such theoretical work to the production of an effective drug, some scientists see APOBEC3G as a promising development in the fight against HIV (San Francisco Chronicle, 7/21).

Back to other news for July 22, 2003