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

doi:https://doi.org/10.1016/j.virol.2011.08.013

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 journal › Article › Academic › peer-review

6 Citations (Scopus)

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 language	English
Pages (from-to)	32-42
Journal	Virology
Volume	420
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2011.08.013
Publication status	Published - 2011

Access to Document

https://doi.org/10.1016/j.virol.2011.08.013

Cite this

@article{7cff168dd56b416eb159945fc4c7b86e,

title = "Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages",

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",

author = "Bol, {Sebastiaan M.} and Thijs Booiman and Bunnik, {Evelien M.} and Moerland, {Perry D.} and {van Dort}, Karel and Strauss, {Jerome F.} and Margit Sieberer and Hanneke Schuitemaker and Kootstra, {Neeltje A.} and {van 't Wout}, {Ang{\'e}lique B.}",

year = "2011",

doi = "https://doi.org/10.1016/j.virol.2011.08.013",

language = "English",

volume = "420",

pages = "32--42",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages

AU - Bol, Sebastiaan M.

AU - Booiman, Thijs

AU - Bunnik, Evelien M.

AU - Moerland, Perry D.

AU - van Dort, Karel

AU - Strauss, Jerome F.

AU - Sieberer, Margit

AU - Schuitemaker, Hanneke

AU - Kootstra, Neeltje A.

AU - van 't Wout, Angélique B.

PY - 2011

Y1 - 2011

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/j.virol.2011.08.013

DO - https://doi.org/10.1016/j.virol.2011.08.013

M3 - Article

C2 - 21920574

SN - 0042-6822

VL - 420

SP - 32

EP - 42

JO - Virology

JF - Virology

IS - 1

ER -