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Resources » Paper

Vekariya U et al. (2018) Life Sci "HIV-1 Nef-POTEE; A novel interaction modulates macrophage dissemination via mTORC2 signaling pathway."

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  • Overview

    PMID:
    30391463
    DOI:
    10.1016/j.lfs.2018.10.068
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00055569

    Vekariya U, Saxena R, Singh P, Rawat K, Kumar B, Kumari S, Agnihotri SK, Kaur S, Sachan R, Nazir A, Bhadauria S, Sachdev M, & Tripathi RK (2018). HIV-1 Nef-POTEE; A novel interaction modulates macrophage dissemination via mTORC2 signaling pathway. Life Sci. doi:10.1016/j.lfs.2018.10.068

    AIMS: Human immunodeficiency virus -1 [HIV-1] Nef, localizes in different cellular compartments and modulates several cellular pathways. Nef promotes virus pathogenicity through alteration in cell surface receptor expression, apoptosis, protein trafficking etc. Nef regulates viral pathogenesis through interaction with different host proteins. Thus, molecular mechanisms of pathogenesis could be deciphered by identifying novel Nef interacting proteins. MAIN METHODS: HIV-1 Nef interacting proteins were identified by pull down assay and MALDI-TOF analysis. The interaction was further validated through mammalian two hybrid assay. Functional role of this interaction was identified by immunoprecipitation assay, cell invasion and cell migration studies. Fold Change in mRNA levels of CD163, CD206, CCL17 and CCL18 was analyzed using qPCR. KEY FINDINGS: In current study, C. elegans protein ACT4C and its human homolog POTEE was identified to be interacting with Nef. This interaction activates mTORC2 complex, which in-turn activates AKT and PKC-. The activation of mTORC2 complex was found to be initiated by the interaction of Nef, mTORC2, Rictor to POTEE. The cellular phenotype and functions affected by Nef-POTEE interaction resulted in significant increase in cell invasion and migration of macrophages (M). SIGNIFICANCE: M is primary target of HIV-1 infection where HIV-1 replicates and polarizes immunosuppressive M2 phenotype. Combine effect of M2 phenotype and Viral-host protein interactions compromise the M associated physiological functions. Infected M dissemination into other system also leads to HIV-1 induced malignancies. Therefore, targeting POTEE-Nef interaction can lead to formulating better therapeutic strategy against HIV-1.

    Authors: Vekariya U, Saxena R, Singh P, Rawat K, Kumar B, Kumari S, Agnihotri SK, Kaur S, Sachan R, Nazir A, Bhadauria S, Sachdev M, Tripathi RK


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