Previously Unidentified Single Nucleotide Polymorphisms in HIV/AIDS Cases Associate with Clinical Parameters and Disease Progression.

Vladimir V Anokhin,Albert A Rizvanov,Svetlana F Khaiboullina,Ekaterina V Martynova,Richard L Tillett,Gulshat R Khasanova,Vincent C Lombardi,Karen A Schlauch,Liliia B Bakhteeva

doi:10.1155/2016/2742648

Abstract

The genetic background of an individual plays an important role in the progression of HIV infection to AIDS. Identifying previously unknown or uncharacterized single nucleotide polymorphisms (SNPs) that associate with disease progression may reveal important therapeutic targets and provide a greater understanding of disease pathogenesis. In the present study, we employed ultra-high multiplex PCR on an Ion Torrent next-generation sequencing platform to sequence 23 innate immune genes from 94 individuals with HIV/AIDS. This data was used to identify potential associations of SNPs with clinical parameters and disease progression. SNPs that associated with an increased viral load were identified in the genes for the interleukin 15 receptor (IL15RA), toll-like receptor 7 (TLR7), tripartite motif-containing protein 5 (TRIM5), and two killer-cell immunoglobulin-like receptors (KIR2DL1 and KIR2DL3). Additionally, SNPs that associated with progression from HIV infection to AIDS were identified in two 2′-5′-oligoadenylate synthetase genes (OAS2 and OAS3). In contrast, other SNPs identified in OAS2 and OAS3 genes, as well as in the TRIM5 and KIR2DS4 genes, were associated with a slower progression of disease. Taken together, our data demonstrates the utility of ultra-high multiplex PCR in identifying polymorphisms of potential clinical significance and further,identifies SNPs that may play a role in HIV pathogenesis.

Highlights

Acquired immunodeficiency syndrome (AIDS) is a devastating disease caused by the human immunodeficiency virus (HIV)
It has been demonstrated that single nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) are associated with an increased susceptibility to infection [8,9,10,11] and are involved in different progressions of HIV/AIDS, a consensus has not been reached
A subsequent study by Soriano-Sarabia et al could not confirm these results, these investigators did identify a polymorphism in TLR9 that was associated with a lower CD4 count and a higher viral load in HIV-positive cases [12]

Summary

Introduction

Acquired immunodeficiency syndrome (AIDS) is a devastating disease caused by the human immunodeficiency virus (HIV). Innate immunity plays an important role in controlling HIV replication [5]. It has been demonstrated that single nucleotide polymorphisms (SNPs) in TLRs are associated with an increased susceptibility to infection [8,9,10,11] and are involved in different progressions of HIV/AIDS, a consensus has not been reached. Papadopoulos et al demonstrated an association between a TLR4 polymorphism and increased risk of opportunistic infection in subjects with advanced HIV-1 infection [8]. A subsequent study by Soriano-Sarabia et al could not confirm these results, these investigators did identify a polymorphism in TLR9 that was associated with a lower CD4 count and a higher viral load in HIV-positive cases [12]

Methods

Results

Discussion

Conclusion