Characterization of APOBEC3 variation in a population of HIV-1 infected individuals in northern South Africa

Abstract

BackgroundThe apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) genes A3D, A3F, A3G and A3H have all been implicated in the restriction of human immunodeficiency virus type 1 (HIV-1) replication. Polymorphisms in these genes are likely to impact viral replication and fitness, contributing to viral diversity. Currently, only a few studies indicate that polymorphisms in the A3 genes may be correlated with infection risk and disease progression.MethodsTo characterize polymorphisms in the coding regions of these APOBEC3 genes in an HIV-1 infected population from the Limpopo Province of South Africa, APOBEC3 gene fragments were amplified from genomic DNA of 192 HIV-1 infected subjects and sequenced on an Illumina MiSeq platform. SNPs were confirmed and compared to SNPs in other populations reported in the 1000 Genome Phase III and HapMap databases, as well as in the ExAC exome database. Hardy-Weinberg Equilibrium was calculated and haplotypes were inferred using the LDlink 3.0 web tool. Linkage Disequilibrium (LD) for these SNPS were calculated in the total 1000 genome and AFR populations using the same tool.ResultsKnown variants compared to the GRCh37 consensus genome sequence were detected at relatively high frequencies (> 5%) in all of the APOBEC3 genes. A3H showed the most variation, with several of the variants present in both alleles in almost all of the patients. Several minor allele variants (< 5%) were also detected in A3D, A3F and A3G. In addition, novel R6K, L221R and T238I variants in A3D and I117I in A3F were observed. Four, five, four, and three haplotypes were identified for A3D, A3F, A3G, and A3H respectively.ConclusionsThe study showed significant polymorphisms in the APOBEC3D, 3F, 3G and 3H genes in our South African HIV1-infected cohort. In the case of all of these genes, the polymorphisms were generally present at higher frequencies than reported in other 1000 genome populations and in the ExAC exome consortium database .Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0740-4) contains supplementary material, which is available to authorized users.

Structural Determinants of the APOBEC3G N-Terminal Domain for HIV-1 RNA Association

“…Naturally occurring non-synonymous changes in the A3G interaction domains are of clinical importance and could alter RNA binding. In this regard, Matume et al recently reported four non-synonymous polymorphisms (H186R, R256H, Q275E, and G363R) in the A3G genes in a cohort of HIV-1 infected South African individuals (Matume et al, 2019). Of these residues, only H186 is present in the A3G-NTD.…”

Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions

“…This has led to an evolutionary “arms race” between hosts and viruses that has left a signature of positive selection, or rapid evolution, in host and viral genes [25]. A3s are highly polymorphic in nature, which greatly influences their viral restriction potential and cancer predisposition [26–28]. There was a significant variation in rs8177832 genotype AA in healthy control and HIV-1-infected subjects in Pakistan (42.25% vs .…”

Human APOBEC3 Variations and Viral Infection

“…They are also diverse in terms of the transcripts (splice variants) they produce. The majority of variations that have been reported for APOBEC3 enzymes are at the DNA level, particularly single nucleotide polymorphisms (SNPs) [ 79 , 80 , 81 , 82 ]. Few studies have also investigated APOBEC3 splicing [ 32 , 83 , 84 , 85 ].…”

“…This enzyme has been suggested to play a role in HIV-1 diversification [ 37 ]. Matume et al analyzed the APOBEC3 polymorphism in 192 HIV-1-infected patients in Northern South Africa, and compared the genotype composition of this cohort with those of the HapMap, 1000 Genomes Project, and ExAC donors [ 80 ]. The study identified several variants of APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H.…”