Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin) restricts the production of a number of enveloped viruses by blocking virus release from the cell surface. This antiviral activity is counteracted by such viral factors as Vpu of human immunodeficiency virus type 1 (HIV-1). Here, we report that Vpu antagonizes human BST-2 but not BST-2 derived from African green monkeys. The determinants of susceptibility to Vpu map to the transmembrane domain of BST-2. In accordance with this, expression of human BST-2 containing a modified transmembrane domain effectively blocks the replication of wild-type Vpuexpressing HIV-1 in CD4 ؉ T cells. Furthermore, these BST-2 variants, as opposed to wild-type human BST-2, are refractory to Vpu-mediated down-regulation as a result of an attenuated interaction with Vpu. In view of the work by others pointing to a key role of the transmembrane domain of Vpu in promoting virus release, our data suggest that a direct interaction through the transmembrane domain of each of these two proteins is a prerequisite for Vpu to down-modulate BST-2.

Helicases hydrolyze nucleotide triphosphates (NTPs) and use the energy to modify the structures of nucleic acids. They are key players in every cellular process involving RNA or DNA. Human immunodeficiency virus type 1 (HIV-1) does not encode a helicase, thus it has to exploit cellular helicases in order to efficiently replicate its RNA genome. Indeed, several helicases have been found to specifically associate with HIV-1 and promote viral replication. However, studies have also revealed a couple of helicases that inhibit HIV-1 replication; these findings suggest that HIV-1 can either benefit from the function of cellular helicases or become curtailed by these enzymes. In this review, we focus on what is known about how a specific helicase associates with HIV-1 and how a distinct step of HIV-1 replication is affected. Despite many helicases having demonstrated roles in HIV-1 replication and dozens of other helicase candidates awaiting to be tested, a deeper appreciation of their involvement in the HIV-1 life cycle is hindered by our limited knowledge at the enzymatic and molecular levels regarding how helicases shape the conformation and structure of viral RNA-protein complexes and how these conformational changes are translated into functional outcomes in the context of viral replication.

RNA helicases are a large family of proteins that rearrange RNA structures and remodel ribonucleic protein complexes using energy derived from hydrolysis of nucleotide triphosphates. They have been shown to participate in every step of RNA metabolism. In the past decade, an increasing number of helicases were shown to promote or inhibit the replication of different viruses, including human immunodeficiency virus type 1. Among these helicases, the DEAD-box RNA helicase DDX17 was recently reported to modulate HIV-1 RNA stability and export. In this study, we further show that the helicase activity of DDX17 is required for the production of infectious HIV-1 particles. Over expression of the DDX17 mutant DQAD in HEK293 cells reduces the amount of packaged viral genomic RNA and diminishes HIV-1 Gag-Pol frameshift. Altogether, these data demonstrate that DDX17 promotes the production of HIV-1 infectious particles by modulating HIV-1 RNA metabolism.