Productive replication of vif-chimeric HIV-1 in feline cells

Melissa A. Stern, Chunling Hu, Dyana T. Saenz, Hind J. Fadel, Olivia Sims, Mary Peretz, Eric M. Poeschla

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Nonprimate animal models of HIV-1 infection are prevented by missing cellular cofactors and by antiviral actions of species-specific host defense factors. These blocks are profound in rodents but may be less abundant in certain Carnivora. Here, we enabled productive, spreading replication and passage of HIV-1 in feline cells. Feline fibroblasts, T-cell lines, and primary peripheral blood mononuclear cells supported early and late HIV-1 life cycle phases in a manner equivalent to that of human cells, except that produced virions had low infectivity. Stable expression of feline immunodeficiency virus (FIV) Vif-green fluorescent protein (GFP) in HIV-1 entry receptor-complemented feline (CrFK) cells enabled robust spreading HIV-1 replication. FIV Vif colocalized with feline APOBEC3 (fA3) proteins, targeted them for degradation, and prevented G→A hypermutation of the HIV-1 cDNA by fA3CH and fA3H. HIV-1 Vif was inactive against fA3s as expected and even paradoxically augmented restriction in some assays. In an interesting contrast, simian immunodeficiency virus SIVmac Vif had substantial anti-fA3 activities, which were complete against fA3CH and partial against fA3H. Moreover, both primate lentiviral Vifs colocalized with fA3s and could be pulled down from cell lysates by fA3CH. HIV-1 molecular clones that encode FIV Vif or SIVmac Vif (HIV-1VF and HIV-1VS) were then constructed. These viruses replicated productively in HIV-1 receptor-expressing CrFK cells and could be passaged serially to uninfected cells. Thus, with the exception of entry receptors, the cat genome can supply the dependency factors needed by HIV-1, and a main restriction can be countered by vif chimerism. The results raise the possibility that the domestic cat could yield an animal model of HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)7378-7395
Number of pages18
JournalJournal of virology
Volume84
Issue number14
DOIs
StatePublished - Jul 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Stern, M. A., Hu, C., Saenz, D. T., Fadel, H. J., Sims, O., Peretz, M., & Poeschla, E. M. (2010). Productive replication of vif-chimeric HIV-1 in feline cells. Journal of virology, 84(14), 7378-7395. https://doi.org/10.1128/JVI.00584-10