Optimal translation initiation enables Vif-deficient human immunodeficiency virus type 1 to escape restriction by APOBEC3G.
APOBEC3G restricts Vif-deficient human immunodeficiency virus type 1 (HIV-1) by deaminating viral cDNA cytosines to uracils. This promutagenic activity is counteracted by HIV-1 Vif, which is a natural APOBEC3G antagonist. However, we previously reported that Vif-deficient HIV-1 could evolve resistance to APOBEC3G by a novel mechanism requiring an A200-to-C/T transition mutation and Vpr inactivation. A pyrimidine at nucleotide 200 in the untranslated leader region contributed to resistance by increasing virus particle production, which resulted in fewer APOBEC3G molecules per particle. Here we show that the A200-to-C/T mutation functions posttranscriptionally by inactivating an upstream start codon, which in turn enables optimal viral mRNA translation from canonical start codons.
Haché
Guylaine
G
Department of Biochemistry, Molecular Biology and Biophysics, Center for Genome Engineering, Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Abbink
Truus E M
TE
Berkhout
Ben
B
Harris
Reuben S
RS
D000071480:APOBEC-3G Deaminase; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D016346:Gene Products, vif / Q000172:deficiency* / Q000235:genetics; D005838:Genotype; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics*
D016346:Gene Products, vif; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase