Fidelity of the reverse transcriptase of human immunodeficiency virus type 2

Mary Bakhanashvili, Amnon Hizi

Research output: Contribution to journalArticlepeer-review

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Abstract

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 Km values rather than by the change in Vmax 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.

Original languageEnglish
Pages (from-to)151-156
Number of pages6
JournalFEBS Letters
Volume306
Issue number2-3
DOIs
StatePublished - 20 Jul 1992
Externally publishedYes

Bibliographical note

Funding Information:
l'or helpful discu~,~ions. Thi~ researcla was supported by Grant NO ROI-AI27035 from the National Institute of Allergy and Infectious Diseases.

Funding

l'or helpful discu~,~ions. Thi~ researcla was supported by Grant NO ROI-AI27035 from the National Institute of Allergy and Infectious Diseases.

FundersFunder number
National Institute of Allergy and Infectious DiseasesR01AI027035

    Keywords

    • DNA synthesis
    • Fidelity
    • HIV
    • Reverse transcriptase

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