Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages

PLOS ONE, February 2011

21364930

Sebastiaan M. Bol, Perry D. Moerland, Sophie Limou, Yvonne van Remmerden, Cédric Coulonges, Daniëlle van Manen, Joshua T. Herbeck, Jacques Fellay, Margit Sieberer, Jantine G. Sietzema, Ruben van 't Slot, Jeremy Martinson, Jean-François Zagury, Hanneke Schuitemaker, Angélique B. van 't Wout

HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages.