Unusual substitutions in HIV‐1 Vif from children infected perinatally without progression to AIDS for more than 8 years without therapy

Abstract

The HIV-1 vif gene encodes for an accessory protein that is central for virus replication due mainly to its capacity to counteract the antiviral action of host APOBEC3 restriction factors. In order to evaluate whether HIV-1 vif alterations account for a delayed progression to AIDS in children infected perinatally, the vif genes from a group of 11 patients who exhibited an extremely slow disease progression (slow progressors) were studied by direct sequencing. In addition, the vif genes from a group of 93 children with typical disease progression (typical progressors) were analyzed for comparison. Phylogenetic analysis indicated that sequences from slow progressors did not have a common origin, discarding a shared ancestor of reduced virulence. There were no differences in the diversity between the vif genes from slow and typical progressors. No gross defects showing a clear distinction among sequences from both groups of children were found. However, in the deduced Vif proteins, changes V13I, V55T, and L81M were observed only in sequences from slow progressors. By analyzing sequences stored in databases, these mutations were determined as unusual substitutions occurring at highly conserved Vif sites across different HIV-1 clades, but were observed with an increased frequency in sequences from elite controllers. These mutations were in the Vif regions reported as relevant for protein activity. These findings suggest that the Vif sequences from slow progressors carry unusual substitutions, which may alter the protein function and may contribute to viral attenuation.

Effects of Korean Red Ginseng and HAART onvifGene in 10 Long-Term Slow Progressors over 20 Years: High Frequency of Deletions and G-to-A Hypermutation

“…In our present study, L81 M [35] and R132S were consistently detected in patient 96-51 and patients 87-05 and 96-51, respectively, although both mutations were found in only in 2 and 3 of 169 Korean patients, respectively. Although the vif gene is highly conserved in HIV-1 genomes, the recovery of hypermutants might be severely underestimated in our present analysis because of the primer mismatching and the difficulties involved in detection following amplification [36, 37].…”

Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

“…Mutations at positions 72 and 77 in Vpr, disrupting the viral protein function, were frequently detected in non-progressors [58, 59]. Finally, single or large insertions in Vpu [60] and amino acid substitutions in Vif [61, 62] have also been associated with non-progression in HIV-1 disease.…”

Immune escape mutations in HIV-1 controllers in the Brazilian Amazon region

“…Phylogenetic analysis of sequences among viremia and nonviremia HIV-1 controllers was performed using the gag gene region. Subtypes B and F were distributed among 16 samples, with no common origin for slow progressor sequences, excluding a possible shared ancestry of reduced virulence [42]. In Brazil, subtype B is most prevalent, followed by subtype F [43,44].…”

“…The vif gene encodes a protein that is central to viral replication because of its ability to neutralize the host's antiviral APOBEC3 protein [42]. Vif optimizes viral replication capacity and acts as an integral component of the reverse transcription complex by serving as a cofactor of the reverse transcriptase enzyme, which is relevant for determining the timeline of progression to AIDS [75].…”