艾滋病毒如何对抗防护药

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.