Viral protein X unlocks the nuclear pore complex through a human Nup153-dependent pathway to promote nuclear translocation of the lentiviral genome

Background Viral protein X (Vpx) is a unique accessory protein encoded by the genome of the Human immunodeficiency virus type 2 (HIV-2) and lineages of the simian immunodeficiency virus of sooty mangabeys. So far, counteracting the cellular restriction factor SAMHD1 and mediating efficient translocation of viral pre-integration complex have been recognized as key functions of Vpx, however, thorough exploration of its effects on the cellular transcriptome and cytokine milieu have not yet been explored.Methods In this study, we carried out transcriptomic analysis of THP-1 cells and determined differential gene expression induced by HIV-2 Vpx, additionally, we analysed the effect of Vpx expression on secretion of key cytokines in the medium of transfected cells.Results Our findings revealed that wild-type HIV-2 Vpx can significantly alter the expression of genes coding for helicases, zinc finger proteins, chaperons, transcription factors and proteins involved in DNA methylation. Differentially altered genes were involved in negative regulation of viral process; type I interferon signaling pathway; DNA-templated transcription, elongation; positive regulation of interferon-beta production and negative regulation of innate immune response. Moreover, Vpx downregulated genes associated with negative regulation of TGF-β1, resulting in stimulation of its production. Importantly, Vpx was also found to decrease the expression of HIV-1 Tat, possibly through downregulation of a crucial splicing factor required for maturation of Tat.Conclusion Transcriptomic analysis revealed that many cellular pathways were affected by HIV-2 Vpx. Studies on cellular cytokine milieu showed that this accessory protein induced key proinflammatory cytokines. Our study provides important information about the complex role played by HIV-2 Vpx in priming and taming the cellular environment to allow for establishment of the infection.

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Viral protein X unlocks the nuclear pore complex through a human Nup153-dependent pathway to promote nuclear translocation of the lentiviral genome

Abstract: MAPK/ERK-2–mediated phosphorylation regulates HIV-2/SIV Vpx interaction with human Nup153, which is critical for altering the nuclear membrane assembly for efficient transport of the lentiviral genome into the nucleus of nondividing target cells.

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References 74 publications

Concise review on optimized methods in production and transduction of lentiviral vectors in order to facilitate immunotherapy and gene therapy

Concise review on optimized methods in production and transduction of lentiviral vectors in order to facilitate immunotherapy and gene therapy

Transcriptomic analysis reveals key pathways influenced by HIV-2 Vpx

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