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Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of innate antiretroviral defense factors.
- Source :
-
Journal of virology [J Virol] 2005 Jul; Vol. 79 (14), pp. 8724-31. - Publication Year :
- 2005
-
Abstract
- Foamy viruses are a family of complex retroviruses that establish common, productive infections in a wide range of nonhuman primates. In contrast, humans appear nonpermissive for foamy virus replication, although zoonotic infections do occur. Here we have analyzed the ability of primate and mouse APOBEC3G proteins to inhibit the infectivity of primate foamy virus (PFV) virions produced in their presence. We demonstrate that several APOBEC3 proteins can potently inhibit the infectivity of a PFV-based viral vector. This inhibition correlated with the packaging of inhibitory APOBEC3 proteins into PFV virions, due to a specific PFV Gag/APOBEC3 interaction, and resulted in the G to A hypermutation of PFV reverse transcripts. While inhibition of PFV virion infectivity by primate APOBEC3 proteins was largely relieved by coexpression of the PFV Bet protein, a cytoplasmic auxiliary protein of previously uncertain function, Bet failed to relieve inhibition caused by murine APOBEC3. PFV Bet bound to human, but not mouse, APOBEC3 proteins in coexpressing cells, and this binding correlated with the specific inhibition of their incorporation into PFV virions. Of note, both PFV Bet and a second Bet protein, derived from an African green monkey foamy virus, rescued the infectivity of Vif-deficient human immunodeficiency virus type 1 (HIV-1) virions produced in the presence of African green monkey APOBEC3G and blocked the incorporation of this host factor into HIV-1 virion particles. However, neither foamy virus Bet protein reduced APOBEC3 protein expression levels in virion producer cells. While these data identify the foamy virus Bet protein as a functional ortholog of the HIV-1 Vif auxiliary protein, they also indicate that Vif and Bet block APOBEC3 protein function by distinct mechanisms.
- Subjects :
- APOBEC-3G Deaminase
Animals
Base Sequence
Cells, Cultured
Cytidine Deaminase
Gene Products, gag metabolism
Humans
Immunity, Innate
Molecular Sequence Data
Mutation
Nucleoside Deaminases
Primates virology
Repressor Proteins
Virus Assembly
HIV-1 immunology
Proteins antagonists & inhibitors
Retroviridae Proteins physiology
Spumavirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 79
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 15994766
- Full Text :
- https://doi.org/10.1128/JVI.79.14.8724-8731.2005