We are studying the impact of mutations and small molecule inhibitors that modulate RT subunit interaction on enzyme function and HIV-1 replication.

Our studies on the molecular determinants of RT dimerization have identified a region in the RT that is critical for RT dimerization, enzyme function and virion RT maturation.

Using the yeast two-hybrid system we have found that nonnucleoside reverse transcriptase inhibitors (NNRTIs) can enhance RT dimerization, which may contribute in part to the inhibitory effect of these drugs.

We are also studying the role of the reverse transcriptase embedded in Gag-Pol on activation of the HIV protease and Gag-Pol processing leading to the production of infectious HIV particles and the role of host cell factors in this process.

Publications

2008

• Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors.
  Sluis-Cremer N, Tachedjian G
  Virus Res. 2008 Jun; 134(1-2):147-156
• Impact of residues in the nonnucleoside reverse transcriptase inhibitor binding pocket on HIV-1 reverse transcriptase heterodimer stability.
  Figueiredo A, Zelina S, Sluis-Cremer N, Tachedjian G
  Curr HIV Res. 2008 Mar; 6(2):130-137

2006

• Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.
  Figueiredo A, Moore KL, Mak J, Sluis-Cremer N, de Bethune MP, Tachedjian G
  PLoS Pathog. 2006 Nov; 2(11):e119
• Dimerization of human immunodeficiency virus type 1 reverse transcriptase as an antiviral target.
  Srivastava S, Sluis-Cremer N, Tachedjian G
  Curr Pharm Des. 2006 Jan; 12(15):1879-1894

2005

• Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer.
  Wapling J, Moore KL, Sonza S, Mak J, Tachedjian G
  J Virol. 2005 Aug; 79(16):10247-10257

2003

• Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization.
  Gilda Tachedjian, Hans-Erik G Aronson, Martha de los Santos, Jas Seehra, John M McCoy, Stephen P Goff
  J Mol Biol. 2003 Feb; 326(2):381-396

2001

• Nonnucleoside reverse transcriptase inhibitors are chemical enhancers of dimerization of the HIV type 1 reverse transcriptase.
  G Tachedjian, M Orlova, S G Sarafianos, E Arnold, S P Goff
  Proc Natl Acad Sci U S A. 2001 Jun; 98(13):7188-7193

2000

• Analysis of mutations and suppressors affecting interactions between the subunits of the HIV type 1 reverse transcriptase.
  G Tachedjian, H E Aronson, S P Goff
  Proc Natl Acad Sci U S A. 2000 Jun; 97(12):6334-6339