title: Dysregulation of autophagy by HIV-1 Nef in human astrocytes.
abstract: Viruses often exploit autophagy, a common cellular process of degradation of damaged proteins, organelles, and pathogens, to avoid destruction. HIV-1 dysregulates this process in several cell types by means of Nef protein. Nef is a small HIV-1 protein which is expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HIV-Associated Neurocognitive Disorders (HAND). In order to explore its effect in the CNS with respect to autophagy, HIV-1 Nef was expressed in primary human fetal astrocytes (PHFA) using an adenovirus vector (Ad-Nef). We observed that Nef expression triggered the accumulation of autophagy markers, ATG8/LC3 and p62 (SQSMT1). Similar results were obtained with Bafilomycin A1, an autophagy inhibitor which blocks the fusion of autophagosome to lysosome. Furthermore co-expression of tandem LC3 vector (mRFP-EGFP-LC3) and Ad-Nef in these cells produced mainly yellow puncta (mRFP+, EGFP+) strongly suggesting that autophagosome fusion to lysosome is blocked in PHFA cells in the presence of Nef. Together these data indicate that HIV-1 Nef mimics Bafilomycin A1 and blocks the last step of autophagy thereby helping HIV-1 virus to avoid autophagic degradation in human astrocytes.
authors.affiliation: a Department of Neuroscience Center for Neurovirology ; Temple University School of Medicine ; Philadelphia , PA USA.
authors.forename: A Sami
authors.initials: AS
authors.lastname: Saribas
authors.affiliation: a Department of Neuroscience Center for Neurovirology ; Temple University School of Medicine ; Philadelphia , PA USA.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.affiliation: a Department of Neuroscience Center for Neurovirology ; Temple University School of Medicine ; Philadelphia , PA USA.
authors.forename: Ilker Kudret
authors.initials: IK
authors.lastname: Sariyer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001253:Astrocytes / Q000473:pathology* / Q000821:virology; D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D015415:Biomarkers / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071190:Autophagy-Related Protein 8 Family; D015415:Biomarkers; C498698:GABARAPL2 protein, human; C477012:MAP1LC3A protein, human; D018942:Macrolides; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C040929:bafilomycin A1
keywords: Adenovirus; Astrocytes; Autophagy; CNS; HIV-1 Nef