Journal of Bacteriology & Parasitology

Misinsertion and mispair extension by human immunodeficiency virus type 1 reverse transcriptase (HIV-1RT) as a mechanism of development of mutations in the viral DNA

7^th World Congress on Microbiology

November 28-29, 2016 Valencia, Spain

Bechan Sharma

University of Allahabad, India

Posters & Accepted Abstracts: J Bacteriol Parasitol

Abstract:

The unique properties of human immunodeficiency virus type 1 reverse trancriptase (HIV-1 RT) include its high propensity for misinsertion and misincorporation of deoxyribonucleotide triphosphate (dNTP) in the growing chainâ??s 3â?? terminus during proviral cDNA synthesis. It was envisaged that the interaction of the side chain of K154 in HIV-1RT with the penultimate nucleotide of the template may be crucial in determination of fidelity of proviral DNA synthesis. This hypothesis was tested by steady-state kinetic studies using wild-type HIV-1 RT and five K154 mutants. These mutants contained replacement of positively charged side chain of lysine with two amino acidsâ?? hydrophobic and two amino acidsâ?? negatively charged side chains. In one of the mutants, the positive charge of Lysine was retained but the side chain was enlarged by one carbon atom while replacing it with arginine. The results indicated variations in their respective activities, extent of formation of binary and ternary complexes as well as in misinsertion and mispair extension of nucleotides in the growing chain of DNA. All of these mutants when tested for their response to 3TC, an approved antiHIV-RT agent, displayed significant resistance to this nucleotide analog when compared to wild type enzyme. The error prone DNA synthesis by HIV-1RT and the development of the antiHIV-1RT drugs resistance may be explained in the light of the three dimensional crystal structure of the enzyme.

Biography :

Email: sharmabi@yahoo.com