Abstract
Viruses interact with multiple host cell factors. Some of these are required to promote viral propagation, others have roles in inhibiting infection. Here, we delineate the function of the cellular factor PHF13 (or SPOC1), a putative HIV-1 restriction factor. Early in the HIV-1 replication cycle PHF13 increased the number of integrated proviral copies and the number of infected cells. However, after HIV-1 integration, high levels of PHF13 suppressed viral gene expression. The antiviral activity of PHF13 is counteracted by the viral accessory protein Vpr, which mediates PHF13 degradation. Altogether, the transcriptional master regulator and chromatin binding protein PHF13 does not have purely repressive effects on HIV-1 replication, but also promotes viral integration. By the functional characterization of the dual role of PHF13 during the HIV-1 replication cycle, we reveal a surprising and intricate mechanism through which HIV-1 might regulate the switch from integration to viral gene expression. Furthermore, we identify PHF13 as a cellular target specifically degraded by HIV-1 Vpr.
Highlights
Viruses hijack and reprogram the host cell machinery in order to achieve optimal viral replication and multiplication
PHF13 represses gene expression of adenovirus and the authors speculated that PHF13 might generally act as a virus restriction factor, including HIV-1 as they observed reduced PHF13 levels in an HIV-1 infected T cell line [23]
The results of this study suggest that PHF13 has opposing effects throughout the HIV-1 replication cycle
Summary
Viruses hijack and reprogram the host cell machinery in order to achieve optimal viral replication and multiplication. Host cells have evolved potent antiviral strategies in order to suppress and restrict virus infection and production, which are designated restriction factors [5]. Host cell factors are often manipulated by HIV-1 accessory proteins (i.e. Nef, Vpu, Vif and Vpr) [6]. These are mostly dispensable for HIV-1 production in cell culture but important for the maintenance of high viral loads and progression to AIDS in vivo. One important function of HIV-1 accessory proteins is to achieve evasion from the host’s immune response for instance by downmodulation of cell surface immune receptors or through counteraction of cellular antiviral restriction factors. Vpr remains one of the most enigmatic HIV-1 accessory proteins [7]
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