Amacker M, Hübscher U
Institute of Veterinary Biochemistry, University of Zürich-Irchel, Switzerland.
J Mol Biol. 1998 May 15;278(4):757-65. doi: 10.1006/jmbi.1998.1739.
The reverse transcriptase (RT) of HIV-1 and feline immunodeficiency virus (FIV) consist of two subunits of 51 kDa (p51) and 66 kDa (p66). In order to elucidate the role of p51 in the heterodimer, chimeric HIV-1/FIV RT heterodimers were constructed and characterized. The FIV RT p51/HIV-1 RT p66 chimera showed a 2.5-fold higher RNase H activity than the natural HIV-1 RT, a 50% lower strand displacement DNA synthesis activity and resistance to the two RT inhibitors 3'-azido-3'-deoxythymidine triphosphate (AZTTP) and Nevirapine. The HIV-1 RT p51/FIV RT p66 chimera on the other hand had very similar properties to the natural FIV RT. The differences observed upon exchange of the p51 subunits suggest that the three-dimensional structure of the p51 subunit in the RT heterodimers is not completely conserved between the human and the feline lentiviruses. Finally, our data suggest an important role for the p51 subunit in maintaining the optimal structural integrity of the RT heterodimer. The different effects of the small subunits on the sensitivity to known RT inhibitors might be of importance in the development of novel drugs against HIV-1 RT.
人类免疫缺陷病毒1型（HIV-1）和猫免疫缺陷病毒（FIV）的逆转录酶（RT）由51 kDa（p51）和66 kDa（p66）的两个亚基组成。为了阐明p51在异源二聚体中的作用，构建并表征了嵌合的HIV-1/FIV RT异源二聚体。FIV RT p51/HIV-1 RT p66嵌合体的核糖核酸酶H活性比天然HIV-1 RT高2.5倍，链置换DNA合成活性低50%，并且对两种RT抑制剂3'-叠氮-3'-脱氧胸苷三磷酸（AZTTP）和奈韦拉平具有抗性。另一方面，HIV-1 RT p51/FIV RT p66嵌合体具有与天然FIV RT非常相似的特性。p51亚基交换后观察到的差异表明，RT异源二聚体中p51亚基的三维结构在人类和猫慢病毒之间并不完全保守。最后，我们的数据表明p51亚基在维持RT异源二聚体的最佳结构完整性方面起着重要作用。小亚基对已知RT抑制剂敏感性的不同影响可能在开发抗HIV-1 RT的新型药物中具有重要意义。
