DExD/H-box helicases in HIV-1 replication and their inhibition

Antiretroviral therapy (ART) reduces human immunodeficiency virus type 1 (HIV-1) infection, but selection of treatment-refractory variants remains a major challenge. HIV-1 encodes 16 canonical proteins, a small number of which are the singular targets of nearly all antiretrovirals developed to date. Cellular factors are increasingly being explored, which may present more therapeutic targets, more effectively target certain aspects of the viral replication cycle, and/or limit viral escape. Unlike most other positive-sense RNA viruses that encode at least one helicase, retroviruses are limited to the host repertoire. Accordingly, HIV-1 subverts DEAD-box helicase 3X (DDX3X) and numerous other cellular helicases of the Asp-Glu-x-Asp/His (DExD/H)-box family to service multiple aspects of its replication cycle. Here we review DDX3X and other DExD/H-box helicases in HIV-1 replication and their inhibition.