Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages.
Virology
; 420(1): 32-42, 2011 Nov 10.
Article
em En
| MEDLINE
| ID: mdl-21920574
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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Infecções por HIV
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HIV-1
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3',5'-AMP Cíclico Fosfodiesterases
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Polimorfismo de Nucleotídeo Único
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Macrófagos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article