Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages

Sebastiaan M. Bol, Thijs Booiman, Evelien M. Bunnik, Perry D. Moerland, Karel van Dort, Jerome F. Strauss, Margit Sieberer, Hanneke Schuitemaker, Neeltje A. Kootstra, Angélique B. van't Wout

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Four genome-wide RNAi screens have recently identified hundreds of HIV-1 dependency factors (HDFs). Previously, we reported a large variation in the ability of HIV-1 to replicate in monocyte-derived macrophages (MDM) derived from >400 healthy seronegative blood donors. Here we determined whether SNPs in genes encoding newly identified HDFs were associated with this variation in HIV-1 replication. We found a significant association between the minor allele of SNP rs2304418 in phosphodiesterase 8A (PDE8A) and lower HIV-1 replication (p=2.4×10-6). The minor allele of SNP rs2304418 was also significantly associated with lower PDE8A mRNA levels in MDM (p=8.3×10-5). In accordance with this, overexpression of PDE8A in HEK293T cells resulted in increased HIV-1 replication, while subsequent knock-down of PDE8A decreased replication. This study links host genetic variation in a newly identified HDF to variation in HIV-1 replication in a relevant primary target cell for HIV-1 and may provide new leads for treatment of this infection.

Original languageEnglish (US)
Pages (from-to)32-42
Number of pages11
JournalVirology
Volume420
Issue number1
DOIs
StatePublished - Nov 10 2011
Externally publishedYes

Keywords

  • HIV-1
  • HIV-1 dependency factor
  • Macrophage
  • PDE8A
  • RNAi
  • SNP

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages'. Together they form a unique fingerprint.

Cite this