Chimeric HIV-1 and feline immunodeficiency virus reverse transcriptases: critical role of the p51 subunit in the structural integrity of heterodimeric lentiviral DNA polymerases

J Mol Biol. 1998 May 15;278(4):757-65. doi: 10.1006/jmbi.1998.1739.


The reverse transcriptase (RT) of HIV-1 and feline immunodeficiency virus (FIV) consist of two subunits of 51 kDa (p51) and 66 kDa (p66). In order to elucidate the role of p51 in the heterodimer, chimeric HIV-1/FIV RT heterodimers were constructed and characterized. The FIV RT p51/HIV-1 RT p66 chimera showed a 2.5-fold higher RNase H activity than the natural HIV-1 RT, a 50% lower strand displacement DNA synthesis activity and resistance to the two RT inhibitors 3'-azido-3'-deoxythymidine triphosphate (AZTTP) and Nevirapine. The HIV-1 RT p51/FIV RT p66 chimera on the other hand had very similar properties to the natural FIV RT. The differences observed upon exchange of the p51 subunits suggest that the three-dimensional structure of the p51 subunit in the RT heterodimers is not completely conserved between the human and the feline lentiviruses. Finally, our data suggest an important role for the p51 subunit in maintaining the optimal structural integrity of the RT heterodimer. The different effects of the small subunits on the sensitivity to known RT inhibitors might be of importance in the development of novel drugs against HIV-1 RT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • DNA, Viral / biosynthesis
  • Dideoxynucleotides
  • Dimerization
  • Drug Resistance, Microbial
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / drug effects
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Immunodeficiency Virus, Feline / enzymology*
  • Immunodeficiency Virus, Feline / genetics
  • Nevirapine / pharmacology
  • Protein Conformation
  • RNA-Directed DNA Polymerase / chemistry*
  • RNA-Directed DNA Polymerase / drug effects
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology
  • Ribonuclease H / metabolism
  • Thymine Nucleotides / pharmacology
  • Zidovudine / analogs & derivatives
  • Zidovudine / pharmacology


  • Antiviral Agents
  • DNA, Viral
  • Dideoxynucleotides
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Inhibitors
  • Thymine Nucleotides
  • Zidovudine
  • zidovudine triphosphate
  • Nevirapine
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase
  • Ribonuclease H