Differential anti-APOBEC3G activity of HIV-1 Vif proteins derived from different subtypes.
Antiretroviral cytidine deaminase APOBEC3G, which is abundantly expressed in peripheral blood lymphocytes and macrophages, strongly protects these cells against HIV-1 infection. The HIV-1 Vif protein overcomes this antiviral effect by enhancing proteasome-mediated APOBEC3G degradation and is key for maintaining viral infectivity. The 579-bp-long vif gene displays high genetic diversity among HIV-1 subtypes. Therefore, it is intriguing to address whether Vif proteins derived from different subtypes differ in their viral defense activity against APOBEC3G. Expression plasmids encoding Vif proteins derived from subtypes A, B, C, CRF01_AE, and CRF02_AG isolates were created, and their anti-APOBEC3G activities were compared. Viruses produced from cells expressing APOBEC3G and Vif proteins from different subtypes showed relatively different viral infectivities. Notably, subtype C-derived Vif proteins tested had the highest activity against APOBEC3G that was ascribed to its increased binding activity, for which the N-terminal domain of the Vif protein sequences was responsible. These results suggest that the biological differences of Vif proteins belonging to different subtypes might affect viral fitness and quasispecies in vivo.
Iwabu
Yukie
Y
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Kinomoto
Masanobu
M
Tatsumi
Masashi
M
Fujita
Hideaki
H
Shimura
Mari
M
Tanaka
Yoshitaka
Y
Ishizaka
Yukihito
Y
Nolan
David
D
Mallal
Simon
S
Sata
Tetsutaro
T
Tokunaga
Kenzo
K
D000071480:APOBEC-3G Deaminase; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014771:Virion / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
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