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Journal of Virology, June 2009, p. 5956-5960, Vol. 83, No. 11
0022-538X/09/$08.00+0 doi:10.1128/JVI.00045-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics,1 Institute for Molecular Virology,2 Center for Genome Engineering, Minneapolis, Minnesota 55455,3 University of Cambridge, Department of Medicine, Cambridge, United Kingdom,4 University of Amsterdam, Laboratory of Experimental Virology, Academic Medical Center, The Netherlands5
Received 8 January 2009/ Accepted 9 March 2009
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.
Published ahead of print on 18 March 2009.
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