title: Signals in APOBEC3F N-terminal and C-terminal deaminase domains each contribute to encapsidation in HIV-1 virions and are both required for HIV-1 restriction.
abstract: Human cytidine deaminases APOBEC3F (A3F) and APOBEC3G (A3G) inhibit human immunodeficiency virus type-1 (HIV-1) replication. In the absence of HIV-1 Vif, A3F and/or A3G are incorporated into assembling virions and exert antiviral functions in subsequently infected target cells. Encapsidation of A3F or A3G within the protease-matured virion core following their incorporation into virions is hypothesized to be important for the antiviral function of these proteins. In this report, we demonstrated that A3F was quantitatively encapsidated in the mature virion core. In distinct contrast, A3G was distributed both within and outside of the virion core. Analysis of a series of A3F-A3G chimeras comprised of exchanged N- and C-terminal deaminase domains identified a 14 amino acid segment in the A3F C-terminal deaminase domain that contributed to preferential encapsidation and anti-HIV activity. Amino acid residue L306 in this C-terminal segment was determined to be necessary, but not sufficient, for these effects. Amino acid residue W126 in the N-terminal deaminase domain was determined also to contribute to preferential encapsidation and antiviral activity of A3F. Analysis of the A3F (W126A L306A) double mutant revealed that both residues are required for full anti-HIV function. The results reported here advance our understanding of the mechanisms of A3F virion encapsidation and antiviral function and may lead to innovative strategies to inhibit HIV-1 replication.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Chisu
authors.initials: C
authors.lastname: Song
authors.forename: Lorraine
authors.initials: L
authors.lastname: Sutton
authors.forename: Megan E
authors.initials: ME
authors.lastname: Johnson
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
authors.forename: John P
authors.initials: JP
authors.lastname: Donahue
mesh_terms: D000071480:APOBEC-3G Deaminase; D019943:Amino Acid Substitution; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D020125:Mutation, Missense; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase