Human immunodeficiency virus type 1 Vif functionally interacts with diverse APOBEC3 cytidine deaminases and moves with them between cytoplasmic sites of mRNA metabolism.
Vif(IIIB), which has been a standard model for the viral infectivity factor of human immunodeficiency virus type 1 (HIV-1), binds the cytidine deaminase APOBEC3G (A3G) and induces its degradation, thereby precluding its lethal incorporation into assembling virions. Additionally, Vif(IIIB) less efficiently degrades A3F, another potent anti-HIV-1 cytidine deaminase. Although the APOBEC3 paralogs A3A, A3B, and A3C have weaker anti-HIV-1 activities and are only partially degraded by Vif(IIIB), we found that Vif(IIIB) induces their emigration from the nucleus to the cytosol and thereby causes net increases in the cytosolic concentrations and anti-HIV-1 activities of A3A and A3B. In contrast, some other Vifs, exemplified by Vif(HXB2) and Vif(ELI-1), much more efficiently degrade and thereby neutralize all APOBEC3s. Studies focused mainly on A3F imply that it occurs associated with mRNA-PABP1 in translationally active polysomes and to a lesser extent in mRNA processing bodies (P-bodies). A3F appears to stabilize the P-bodies with which it is associated. A correspondingly small proportion of Vif(IIIB) also localizes in P-bodies in an A3F-dependent manner. Stress causes A3A, A3B, A3C, and A3F to colocalize efficiently with Vif(IIIB) and mRNA-PABP1 complexes in stress granules in a manner that is prevented by cycloheximide, an inhibitor of translational elongation. Coimmunoprecipitation studies suggest that Vifs from different HIV-1 isolates associate with all tested APOBEC3s. Thus, Vifs interact closely with structurally diverse APOBEC3s, with effects on their subcellular localization, degradation rates, and antiviral activities. Cytosolic APOBEC3-Vif complexes are predominantly bound to mRNAs that dynamically move between translationally active and storage or processing pools.
Marin
Mariana
M
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239-3098, USA.
Golem
Sheetal
S
Rose
Kristine M
KM
Kozak
Susan L
SL
Kabat
David
D
D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D039122:Poly(A)-Binding Protein I / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D015778:Minor Histocompatibility Antigens; D039122:Poly(A)-Binding Protein I; D011506:Proteins; D012333:RNA, Messenger; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; C121399:APOBEC3A protein, human; C495794:APOBEC3B protein, human; C495795:APOBEC3C protein, human; D003564:Cytidine Deaminase