title: Equal amounts of intracellular and virion-enclosed hepatitis C virus RNA are associated with peripheral-blood mononuclear cells in vivo.
abstract: BACKGROUND
  Hepatitis C virus (HCV) replicating in peripheral-blood mononuclear cells (PBMCs) may represent an extrahepatic viral reservoir. Quantitation of HCV RNA with regard to its subcellular distribution and longitudinal course is needed for better understanding of the largely unexplored in vivo dynamics and potential pathogenetic significance of HCV in PBMCs.
  
  
  METHODS
  Plasma and PBMCs from 30 patients coinfected with HCV and human immunodeficiency virus were evaluated in cross-sectional and longitudinal analyses, for up to 40 months. Differential extraction of virion-enclosed HCV RNA associated with cells was performed in parallel with extraction of total cellular HCV RNA. HCV RNA of either orientation was quantified by real-time polymerase chain reaction.
  
  
  RESULTS
  HCV RNA was detected only in PBMCs from patients with viremia and at relatively stable quantities over time. Intracellular HCV RNA corresponding to ~60% of total cellular HCV RNA was strongly correlated with virion-enclosed HCV RNA but was only weakly associated with viral loads in plasma. In contrast, the ratio of HCV RNA load in PBMCs versus that in plasma was patient specific and stable over time.
  
  
  CONCLUSIONS
  The substantial and patient-specific amounts of intracellular HCV RNA found by the present study support a concept of low-level replication in PBMCs. There was no evidence for persistent HCV infection in PBMCs after clearance of viremia in plasma.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 8032 Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kaiser
authors.forename: Barbara
authors.initials: B
authors.lastname: Niederost
authors.forename: Beda
authors.initials: B
authors.lastname: Joos
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Milos
authors.initials: M
authors.lastname: Opravil
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Gunthard
authors.forename: Marek
authors.initials: M
authors.lastname: Fischer
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood / Q000235:genetics; D019562:Viral Load; D014771:Virion / Q000235:genetics*
chemical_list: D012367:RNA, Viral