title: Autophagy protects cells from HCV-induced defects in lipid metabolism.
abstract: OBJECTIVE
  Autophagy is a lysosome-mediated catabolic process that mediates degradation and recycling of all major components of eukaryotic cells. Different stresses, including viral and bacterial infection, induce autophagy, which can promote cell survival by removing the stress inducer or by attenuating its dangerous effects. High levels of autophagy occur during infection of cells with hepatitis C virus (HCV), but the clinical relevance of this process is not clear.
  
  
  METHODS
  Levels of autophagy were analyzed in liver biopsy samples from 22 patients with HCV infection using microtubule-associated protein-1 light chain 3 immunoblotting; associations with histological and metabolic parameters were evaluated by Pearson correlation analysis. We investigated the role of HCV-induced autophagy in lipid degradation in cells infected with the virus or replicons, and analyzed autophagosome contents by confocal microscopy and by measuring lipid levels after inhibition of autophagy by Beclin 1 knockdown or lysosome inhibitors.
  
  
  RESULTS
  In liver biopsy samples from patients with HCV, there was an inverse correlation between microvesicular steatosis and level of autophagy (r = -0.617; P = .002). HCV selectively induced autophagy of lipids in virus-infected and replicon cells. In each system, autophagosomes frequently colocalized with lipid deposits, mainly formed by unesterified cholesterol. Inhibition of the autophagic process in these cells significantly increased the induction of cholesterol accumulation by HCV.
  
  
  CONCLUSIONS
  Autophagy counteracts the alterations in lipid metabolism induced by HCV. Disruption of the autophagic process might contribute to development of steatosis in patients with HCV.
authors.affiliation: National Institute for Infectious Diseases IRCCS L. Spallanzani, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vescovo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romagnoli
authors.forename: Ariel Basulto
authors.initials: AB
authors.lastname: Perdomo
authors.forename: Marco
authors.initials: M
authors.lastname: Corazzari
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ciccosanti
authors.forename: Tonino
authors.initials: T
authors.lastname: Alonzi
authors.forename: Roberta
authors.initials: R
authors.lastname: Nardacci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
authors.forename: Carmelo
authors.initials: C
authors.lastname: Garcia-Monzon
authors.forename: Oreste
authors.initials: O
authors.lastname: Lo Iacono
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D001706:Biopsy; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D019610:Cytoprotection; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007558:Italy; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D012093:Replicon; D012189:Retrospective Studies
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D002784:Cholesterol