HIV-1 Nef-POTEE; A novel interaction modulates macrophage dissemination via mTORC2 signaling pathway

Publication date: Available online 31 October 2018Source: Life SciencesAuthor(s): Umeshkumar Vekariya, Reshu Saxena, Poonam Singh, Kavita Rawat, Balawant Kumar, Sushila Kumari, Saurabh Kumar Agnihotri, Supinder Kaur, Rekha Sachan, Aamir Nazir, Smrati Bhadauria, Monika Sachdev, Raj Kamal TripathiAbstractAimsHuman 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 methodsHIV-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 findingsIn 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-α. The activation of mTORC2 complex was found to be initiated by the interaction of Nef, mTORC2, Rictor to POTEE. The cellular phenotype and functions af...
Source: Life Sciences - Category: Biology Source Type: research