Lentiviral Vpx induces alteration of mammalian cell nuclear envelope integrity

Abstract

Vpx, a virion-associated protein of Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) counteracts host restriction factor SAMDH1 for efficient viral DNA synthesis in the cytoplasm and mediates subsequent nuclear translocation of the viral genome. Vpx was found to be indispensable in the viral infection of terminally differentiated target cells and macaques infected with virions carrying truncated Vpx showed delayed pathogenesis, suggesting multiple roles of Vpx at different steps in the virus life cycle. The current study demonstrates a novel function of SIVsmPBj1.9 Vpx on the integrity of the nuclear envelope in HeLa cells. Results from the Super-Resolution Structured Illumination Microscopy (SR-SIM) analysis showed that Vpx puncta alter HeLa cell nuclear envelope assembly. Furthermore, three-dimensional (3D) SIM analysis of such regions suggests that Vpx is primed in a specific way to disrupt the nuclear envelope integrity. The nuclear incursion of cytoplasmic proteins through Vpx mediated ruptured nuclear envelope regions suggest that these events might play a critical role in the nuclear entry of otherwise cytoplasmically sequestered molecules and theirby may be assisting Vpx functions including the transport of viral genome into the nucleus, which is critical for the establishment of virus infection and pathogenesis.