Rutgers researchers have discovered how HIV-1, the virus that causes AIDS, resists AZT, a drug widely used to treat AIDS. The scientists, who report their findings in Nature Structural1 & Molecular2 Biology, believe their discovery helps researchers understand how important anti-AIDS treatments can fail and could help AIDS researchers develop more effective treatment for the disease.
"What we've found is the detailed3 way in which the mutations act to promote the resistance," said author Eddy4 Arnold, Board of Governors Professor of Chemistry and Chemical Biology, and a resident faculty5 member of the Center for Advanced Biotechnology and Medicine. "Instead of blocking the actions of AZT, the virus actually removes it, and it does so by using ATP, one of the most common cellular6 molecules7. This is an outstanding example of how sneaky(鬼鬼祟祟的) HIV can be in thwarting8(阻挠,妨碍) the efficacy of therapeutic9 drugs."
AZT was once the only treatment for AIDS, and it remains10 an important treatment, particularly in preventing the transmission of the virus from infected mothers to their unborn children.
Researchers knew almost from the beginning that the virus developed resistance to AZT, and that this resistance had to do with mutations, but the way the mutations worked to resist the drug was mysterious.
AZT works by inhibiting11(抑制,约束) an enzyme12, reverse transcriptase(逆转录酶) , which HIV needs to produce DNA13 from RNA, and thus replicate14 itself. About 10 years ago, biochemical studies in several laboratories established that AZT-resistant HIV-1 reverse transcriptase uses adenosine triphosphate(三磷酸腺苷) , or ATP, which moves energy around inside the cell, to remove the AZT. Arnold and his co-authors have used X-ray crystallography(结晶学) to describe in atomic detail how the AZT-resistance mutations allow reverse transcriptase to recruit ATP to remove the AZT.