Epigenetic dissection of human genetic variation in HIV infection

Epigenetic dissection of human genetic variation in HIV infection

Project

Host genetic variation has long been recognized to play a major role in HIV-1 infection susceptibility and disease progression. It is widely accepted that genetic variants in loci encoding class I human leukocyte antigens (HLA) and the chemokine receptor CCR5 have a major impact on HIV infection. The contribution of additional genetic variants remains elusive. In the past decade genome wide association studies (GWAS) have identified many single nucleotide polymorphisms that are statistically correlated with several aspects of HIV disease progression. The significance of these genetic variants is currently not clear since the studies lack statistical power and many of the correlated variants locate to non-coding regions of the genome with unknown function. Previous studies comparing GWAS data with data obtained genome wide mapping of chromatin features have found that many phenotype associated SNPs locate to gene regulatory elements. This study will functionally characterize HIV associated non-coding SNPs. In particular it will test whether these SNPs alter the long-range transcriptional regulation of genes that could modulate the susceptibility to HIV infection. This study will provide mechanistic and functional insight into the contribution of host genetic variation to HIV infection and will identify novel disease-related target genes for therapy.

Project details

Time frame
31 July 2016 - 31 July 2019
Budget
€ 275,000
Active in
Netherlands

Objectives

This study will functionally characterize HIV associated non-coding SNPs. In particular it will test whether these SNPs alter the long-range transcriptional regulation of genes that could modulate the susceptibility to HIV infection. This study will provide mechanistic and functional insight into the contribution of host genetic variation to HIV infection and will identify novel disease-related target genes for new therapies, vaccination strategies and diagnostic tools.
Specific research questions:
1. Do HIV associated SNPs locate to regulatory regions of the genome?
2.Which genes are controlled by these regulatory regions?
3. How do these genes contribute to the establishment and progression of HIV? Do the expression levels of genes that are controlled by the SNP containing regulatory elements indeed correlate with HIV infection?
4. What is the mechanism of attenuated regulation of the SNP containing regulatory elements? Which transcription factor binding sites are disrupted and what is the consequence of the altered binding of these transcription factors?
Output: all answers will be integrated into scientific publications.

Community groups

0, there are no direct endusers of this project.
The enduses could be interpreted as the scientific community.

Background

Host genetic variation has long been recognized to play a major role in HIV-1 infection susceptibility and disease progression. It is widely accepted that genetic variants in loci encoding class I human leukocyte antigens (HLA) and the chemokine receptor CCR5 have a major impact on HIV infection. The contribution of additional genetic variants remains elusive.

In the past decade genome wide association studies (GWAS) have identified many single nucleotide polymorphisms that are statistically correlated with several aspects of HIV disease progression. The significance of these genetic variants is currently not clear since the studies lack statistical power and many of the correlated variants locate to non-coding regions of the genome with unknown function. Previous studies comparing GWAS data with data obtained genome wide mapping of chromatin features have found that many phenotype associated SNPs locate to gene regulatory elements.

Goals

Everyone living with HIV worldwide receives treatment
100%
Contributed within this project

Other projects within the programme

HIV envelope trimer vaccines that engage desirable germline antibodies

Despite 30 years of intensive research, an effective HIV-1 vaccine remains elusi...

Investigation of the central nervous system as a potential HIV reservoir during combination antiretroviral therapy.

The major obstacle to HIV cure is presence of a stable reservoir of latently inf...

2015 - 2016 RfP - Scientific Research

This project is part of 2015 - 2016 RfP - Scientific Research

Aidsfonds.org uses cookies to offer the best website experience possible and to anonymously analyze website behaviour. More information.