Stably expressed APOBEC3F has negligible antiviral activity.
APOBEC3F (A3F) is a member of the family of cytidine deaminases that is often coexpressed with APOBEC3G (A3G) in cells susceptible to HIV infection. A3F has been shown to have strong antiviral activity in transient-expression studies, and together with A3G, it is considered the most potent cytidine deaminase targeting HIV. Previous analyses suggested that the antiviral properties of A3F can be dissociated from its catalytic deaminase activity. We were able to confirm the deaminase-independent antiviral activity of exogenously expressed A3F; however, we also noted that exogenous expression was associated with very high A3F mRNA and protein levels. In analogy to our previous study of A3G, we produced stable HeLa cell lines constitutively expressing wild-type or deaminase-defective A3F at levels that were more in line with the levels of endogenous A3F in H9 cells. A3F expressed in stable HeLa cells was packaged into Vif-deficient viral particles with an efficiency similar to that of A3G and was properly targeted to the viral nucleoprotein complex. Surprisingly, however, neither wild-type nor deaminase-defective A3F inhibited HIV-1 infectivity. These results imply that the antiviral activity of endogenous A3F is negligible compared to that of A3G.
Miyagi
Eri
E
Viral Biochemistry Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bldg. 4, Room 310, 4 Center Drive MSC 0460, Bethesda, MD 20892-0460, USA.
Brown
Charles R
CR
Opi
Sandrine
S
Khan
Mohammad
M
Goila-Gaur
Ritu
R
Kao
Sandra
S
Walker
Robert C
RC
Hirsch
Vanessa
V
Strebel
Klaus
K
D000071480:APOBEC-3G Deaminase; D003564:Cytidine Deaminase / Q000276:immunology*; D043525:Cytosine Deaminase / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections; D015497:HIV-1 / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D014771:Virion; D054320:vif Gene Products, Human Immunodeficiency Virus
D012333:RNA, Messenger; D054320:vif Gene Products, Human Immunodeficiency Virus; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase