Journal of Antivirals & Antiretrovirals
Open Access

Mutant tRNA - A novel alternative approach for enhanced inhibition of HIV-1 replication

2^nd International Conference on Retroviruses and Novel Drugs

June 30-July 01, 2016 Cape Town, South Africa

Yuanan Lu

Department of Public Health Sciences, University of Hawaii, USA

Posters & Accepted Abstracts: J Antivir Antiretrovir

Abstract :

Host derived cellular tRNALys3 plays an essential role in the HIV-1 replication as a primer to initiate the synthesis of viral cDNA during reverse transcription. As a consequence, this tRNA primer has constituted as an attractive potential target for anti-HIV-1 intervention. Previous in vitro experiments demonstrated that the 1st generation of mutant tRNALys3 with limited substitution of nucleotides in the 3��? terminus led to aberrant reverse transcription from designed TAR site and detectable inhibition of HIV-1 replication. However, the mutant tRNA Lys3 could also direct the reverse transcription at the normal primer-binding site (PBS) with potentially weakened inhibition of HIV-1 infection. To achieve more patent inhibition of HIV-1 replication, a series of 2nd generation of mutant tRNALys3 were constructed with extended lengths of nucleotide substitutions or by targeting different viral genome sites. Following stable transduction and expression of newly constructed mutant tRNALys3 in human T-cells, a positive correlation was determined between the length of mutation in the 3��? PBS-binding region of tRNALys3 and the specificity of HIV-1 reverse transcription initiation from the target site and associated inhibitory effect on HIV-1 replication. Moreover, in vitro expression of two mutant tRNALys3 targeting the Int-encoding region and Env gene, respectively, both showed a high anti-HIV-1 activity, suggesting that not only the TAR, but other distant sites downstream of the PBS could be effectively targeted by mutant tRNALys3. In addition, this in vitro test demonstrated that increased production of mutant tRNALys3 through transducing the T-cells with multiple-copy of mutant tRNA Lys3 expression cassettes further enhanced the potency of mutant tRNA-mediated anti-HIV-1 activity. These new findings lay ground for more in-depth studies at both in vitro and in vivo settings in future and support the intervention of the HIV-1 genome conversion through mutant tRNALys3 as an effective alternative approach to the current anti-HIV-1 regimens.

Biography :

Email: yuanan@hawaii.edu