Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9878-82.

Chimeric human immunodeficiency virus type 1/type 2 reverse transcriptases display reversed sensitivity to nonnucleoside analog inhibitors.

Shih CK, Rose JM, Hansen GL, Wu JC, Bacolla A, Griffin JA.

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Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.

Abstract

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), an important therapeutic target in the treatment of AIDS, is effectively inhibited by a class of nonnucleoside analog compounds that includes nevirapine (BI-RG-587) and tetrahydroimidazo[4,5,1-jk]-[1,4]benzodiazepin-2(1H)-one and -thione. We show that both tyrosine residues at positions 181 and 188 flanking the putative catalytic site of HIV-1 RT are required for sensitivity of the enzyme to these compounds. HIV-2 RT, which does not have tyrosines at these positions, is resistant to these nonnucleoside analog inhibitors. Substitution of the HIV-2 RT amino acid residues at position 181 or 188 into HIV-1 RT results in an enzyme that is resistant to these compounds while retaining sensitivity to 3'-azido-2',3'-dideoxythymidine triphosphate. HIV-2 RT substituted with amino acids 176-190 from HIV-1 RT acquires sensitivity to these nonnucleoside analog inhibitors.

PMID:: 1719542; [PubMed - indexed for MEDLINE]
PMCID: PMC52824

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Chimeric human immunodeficiency virus type 1/type 2 reverse transcriptases display reversed sensitivity to nonnucleoside analog inhibitors.

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