Mutation Vif-22H, which allows HIV-1 to use the APOBEC3G hypermutation to develop resistance, could appear more quickly in certain non-B variants

Abstract

Sir, HIV-1 Vif protein counteracts the lethal hypermutation produced by the cellular antiviral factor APOBEC3G (A3G) in HIV-1. This effect consists of a cytidine deamination of the HIV-1 cDNA that results in guanosine to adenosine (G-to-A) substitutions in the proviral sequences in a GG-to-GA dinucleotide context. However, in defective Vif alleles these G-to-A substitutions could benefit the virus, promoting sequence diversification even in drug resistance sites, and therefore accelerate the evolution of resistance and immune escape. It would represent a new mechanism of viral escape from antiretrovirals and a suitable target for drug development. In this context, the mutation Vif-K22H (located in the Vif–A3G interaction domain) has been recently identified as a key mutation to trigger this mechanism in subjects under therapy failure. However, all the described Vif-K22H samples were subtype B. Most studies are based on this subtype because it is prevalent in developed regions, despite the worldwide predominance of HIV-1 non-B variants, a term that includes the remaining subtypes and inter-subtype recombinants. Here we analyse the presence of Vif-K22H in the most prevalent HIV-1 non-B subtypes and recombinants, which, up to now, is still unknown. All HIV-1 vif sequences (n1⁄42895) ascribed to pure subtypes and recombinants CRF01_AE and CRF02_AG were downloaded from the Los Alamos National Laboratory Database (LANL-DB) in March 2010: 143 A1; 5 A2; 1690 B; 546 C; 91 D; 36 F1; 4 F2; 30 G; 4 H; 3 J; 2 K; 242 CRF01_AE; and 99 CRF02_AG. Nucleotide and amino acid variability in Vif-22 across all HIV-1 studied subtypes and recombinants was identified and compared (Table 1). Table 1. Amino acid and nucleotide variability at position 22 among the 2895 vif sequences deposited in the LANL-DB according to HIV-1 clade