Potent lentiviral restriction by a synthetic feline TRIM5 cyclophilin A fusion

J Virol. 2010 Sep;84(17):8980-5. doi: 10.1128/JVI.00858-10. Epub 2010 Jun 16.

Abstract

A synthetic feline TRIM5-cyclophilin A fusion protein (feTRIMCyp) was generated and transduced into feline cells. feTRIMCyp was highly efficient at preventing infection with human (HIV) and feline (FIV) immunodeficiency virus pseudotypes, and feTRIMCyp-expressing cells resisted productive infection with either FIV-Fca or FIV-Pco. The restriction of FIV infection by feTRIMCyp was reversed by the cyclosporine (Cs) derivatives NIM811 and Debio-025 but less so by Cs itself. FeTRIMCyp and FIV infections of the cat offer a unique opportunity to evaluate TRIMCyp-based approaches to genetic therapy for HIV infection and the treatment of AIDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / chemical synthesis
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cats
  • Cell Line
  • Cyclophilin A / chemical synthesis
  • Cyclophilin A / genetics
  • Cyclophilin A / metabolism*
  • Disease Models, Animal
  • Feline Acquired Immunodeficiency Syndrome / prevention & control
  • Feline Acquired Immunodeficiency Syndrome / virology*
  • HIV Infections / prevention & control
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • Humans
  • Immunodeficiency Virus, Feline / physiology*
  • Recombinant Fusion Proteins / chemical synthesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Virus Internalization*

Substances

  • Carrier Proteins
  • Recombinant Fusion Proteins
  • Tripartite Motif Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • Cyclophilin A