A HIV-1 minimal gag protein is superior to nucleocapsid at in vitro annealing and exhibits multimerization-induced inhibition of reverse transcription

J Biol Chem. 2005 Apr 29;280(17):17488-96. doi: 10.1074/jbc.M501310200. Epub 2005 Feb 24.

Abstract

HIV-1 uses tRNA3Lys to prime reverse transcription of its viral RNA. In this process, the 3'-end of tRNA3Lys must be annealed to the primer binding site of HIV-1 genomic RNA, and the two molecules together form a complex structure. During annealing, the nucleocapsid (NC) protein enhances the unwinding of tertiary structures within both RNA molecules. Moreover, the packaging of tRNA3Lys occurs prior to viral budding at a time when NC is still part of the Pr55Gag polyprotein. In contrast, Pr55Gag is able to produce virus-like particles on its own. We have recently shown that an N-terminal extended form of NC (mGag), containing all of the minimal elements required for virus-like particle formation, possesses greater affinity for HIV-1 genomic RNA than does NC alone. We have now studied the tRNA3Lys-annealing properties of mGag in comparison to those of NC and report that the former is more efficient in this regard than the latter. We have also tested each of a mutant version of mGag, an extended form of mGag, and an almost full-length form of Gag, and showed that all of these possessed greater tRNA-annealing capacity than did the viral NC protein. Yet, surprisingly, multimerization of Gag-related proteins did not abrogate this annealing process but rather resulted in dramatically reduced levels of reverse transcriptase processivity. These results suggest that the initial stages of reverse transcription may be regulated by the multimerization of Pr55Gag polyprotein at times prior to the cleavage of NC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • DNA Primers / chemistry
  • Dimerization
  • Dose-Response Relationship, Drug
  • Gene Products, gag / chemistry*
  • Gene Products, gag / physiology*
  • HIV-1 / metabolism*
  • Hot Temperature
  • In Vitro Techniques
  • Models, Biological
  • Models, Genetic
  • Mutation
  • Nucleic Acid Conformation
  • Nucleocapsid / chemistry*
  • Polymerase Chain Reaction
  • Protein Binding
  • Protein Folding
  • Protein Precursors / chemistry*
  • Protein Precursors / physiology*
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • RNA / chemistry
  • RNA, Transfer / chemistry
  • RNA, Transfer, Amino Acyl / chemistry*
  • Transcription, Genetic*

Substances

  • DNA Primers
  • Gene Products, gag
  • Protein Precursors
  • Proteins
  • RNA, Transfer, Amino Acyl
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • RNA
  • DNA
  • RNA, Transfer