Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity

J Virol. 2002 Aug;76(15):7560-70. doi: 10.1128/jvi.76.15.7560-7570.2002.


Foamy virus (FV) replication is resistant to most nucleoside analog reverse transcriptase (RT) inhibitors. In an attempt to create a 2',3'-dideoxy-3'-thiacytidine (3TC)-sensitive virus, the second residue in the highly conserved YXDD motif of simian foamy virus-chimpanzee (human isolate) [SFVcpz(hu)] RT was changed from Val (V) to Met (M). Unexpectedly, the resultant virus, SFVcpz(hu) RT-V313M, replicated poorly, and Met rapidly reverted to Val. Despite the presence of approximately 50% of wild-type RT activity in RT-V313M virions, full-length DNA products were not detected in transfected cells. Using purified recombinant enzymes, we found that the wild-type FV RT is significantly more processive than human immunodeficiency virus type 1 RT. However, the V313M mutant has about 40% of the wild-type level of FV RT activity and has a lower processivity than the wild-type FV enzyme. The V313M mutant RT is also relatively resistant to 3TC. These results suggest that the decrease in RT activity and processivity of FV RT-V313M prevents completion of reverse transcription and greatly diminishes viral replication.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Catalytic Domain / genetics*
  • Catalytic Domain / physiology
  • Cell Line
  • Cricetinae
  • HIV Reverse Transcriptase / metabolism
  • Humans
  • Mutation*
  • Pan troglodytes
  • RNA-Directed DNA Polymerase / chemistry
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology
  • Spumavirus / drug effects
  • Spumavirus / enzymology*
  • Spumavirus / pathogenicity*
  • Spumavirus / physiology
  • Transcription, Genetic
  • Virion / metabolism
  • Virus Replication


  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase