Fidelity of the reverse transcriptase of human immunodeficiency virus type 2

FEBS Letters

Hizi, Amnon¹  Bakhanashvili, Mary¹ 

[1] Department of Cell Biology and Histology, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

关键词: Fidelity;    DNA synthesis;    HIV;    Reverse transcriptase;   

DOI  :  10.1016/0014-5793(92)80988-S

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The relatively low fidelity of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) was implicated as a major factor that contributes to the genetic variability of the virus. Extension of mismatched 3′ termini of the primer DNA was shown to be a major determinant of the infidelity of HIV-1 RT. Human immunodeficiency virus type 2 (HIV-2) also shows extensive genetic variations. Therefore, we have analyzed the fidelity of the DNA-dependent DNA polymerase activity of HIV-2 RT and compared it with those of RTs of HIV-1 and murine leukemia virus (MLV). Like other retroviral RTs, the HIV-2 RT was shown to lack a 3′→5′ exonuclease activity. The ability of HIV-2 RT to extend preformed 3′-terminal A:A, A:C and A:G mispairs was examined by quantitating the amount and length of extended primers. The results demonstrate a relatively efficient mispair extension by HIV-2 RT with a specificity of A:C⪢A:A>A:G. The mispair extension appears to be affected mainly by the increase of apparent K _m values rather than by the change in V _max values. The relative extension frequencies from all mispairs with HIV-1 and HIV-2 RTs was 6- to 9-fold greater than that of MLV RT, suggesting that the HIV enzymes are substantially more error-prone than MLV RT.

【 授权许可】

Unknown