Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

This article is part of the supplement: Frontiers of Retrovirology 2011

Open Access Oral presentation

Polymorphism in HIV-1 dependency factor PDE8A affects gene expression and HIV-1 replication in primary macrophages

Thijs Booiman1*, Sebastiaan Bol1, Evelien Bunnik1, Perry Moerland2, Karel van Dort1, Jerome Strauss3, Margit Síeberer1, Hanneke Schuitemaker1, Neeltje Kootstra1 and Angélique van't Wout1

  • * Corresponding author: Thijs Booiman

Author Affiliations

1 Department of Experimental Immunology, Academic Medical Center of the University of Amsterdam, Amsterdam, 1105AZ, The Netherlands

2 Department Bioinformatics, Academic Medical Center of the University of Amsterdam, Amsterdam, 1 105AZ, The Netherlands

3 Department of Obstetrics and Gynecology, Virginia Commonwealth University, School of Medicine, Richmond, VA, 23298, USA

For all author emails, please log on.

Retrovirology 2011, 8(Suppl 2):O37  doi:10.1186/1742-4690-8-S2-O37

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/8/S2/O37


Published:3 October 2011

© 2011 Booiman et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

The limited size of the human immunodeficiency virus 1 (HIV-1) genome and the small number of proteins it encodes make the virus highly dependent on host proteins for its replication. Four genome-wide RNAi screens have recently identified a large number of HIV-1 dependency factors (HDFs), with the majority of these proteins never before associated with HIV-1 replication. Recently, we reported more than 3 log variation in the ability of HIV-1 to replicate in monocyte derived macrophages (MDM) derived from >4OO healthy seronegative blood donors. In our present study we determined whether single nucleotide polymorphisms (SNPs) in the genes encoding the newly identified HDFs were associated with this variation in HIV-1 replication.

Materials and methods

DNA from Caucasian donors whose MDM had low (n=96) or high (n=96) viral Gag p24 production, was used for genome-wide SNP genotyping. Linear regression assuming an additive model was used to test for association between the genotype of HDF SNPs and HIV-1 replication in MDM.

Results

We found a significant association between the minor allele of SNP rs2304418 located in the phosphodiesterase 8a (PDE8A) gene and lower HIV-1 replication (p=2.4×10-6), even after correction for multiple testing. This finding was independent of the CCR5 Δ32 genotype. The minor allele of SNP rs2304418 was also significantly associated with lower PDE8A mRNA levels in MDM (p=8.3×10-5) and PDE8A mRNA levels correlated with HIV-1 replication. Resequencingof the promotor and untranslated regions of the PDE8A mRNA did not reveal novel SNPs likely to be the causative variant.

Conclusions

Our finding is in agreement with the reported finding that RNAi knock-down of PDE8A resulted in lower HIV-1 replication. PDE8A is highly expressed in macrophages and specifically catalyzes the hydrolysis of cAMP to AMP. We are currently investigating at which level of the virus life cycle PDE8A affects HIV-1 replication.