Optimal translation initiation enables Vif-deficient human immunodeficiency virus type 1 to escape restriction by APOBEC3G

Guylaine Haché, Truus E.M. Abbink, Ben Berkhout, Reuben S. Harris

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)5956-5960
Number of pages5
JournalJournal of Virology
Volume83
Issue number11
DOIs
Publication statusPublished - Jun 2009

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