title: Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: compartmentalized regulation of SIV.
abstract: BACKGROUND
  Before the onset of AIDS, replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) in the lungs is considered to be latent. When and how virus replication is controlled in the lungs is unclear. In the present study, we examine virus replication in the lungs and in cells recovered from bronchoalveolar lavage (BAL) samples in a comprehensive, longitudinal analysis of an SIV/macaque model.
  
  
  METHODS
  Gene-specific RNA and DNA were quantitated by polymerase chain reaction (PCR) and by real-time reverse-transcription PCR (RT-PCR). Alveolar macrophages were isolated using Dynabeads CD14 (Invitrogen). Expression of CCAAT/enhancer-binding protein beta (C/EBP beta ) isoforms was examined by Western blot analysis.
  
  
  RESULTS
  SIV replication occurred in the lungs during acute infection and correlated with plasma viral load. Innate immune responses involving interferon- beta and the dominant-negative isoform of C/EBP beta were induced at this time. SIV RNA expression was suppressed in the lungs during asymptomatic infection, when no correlation existed with plasma viral load until SIV RNA levels rebounded again during late-stage disease. Modulation of viral RNA levels in BAL cells reflected RNA levels in lung tissue throughout each phase of infection.
  
  
  CONCLUSIONS
  Quantitation of SIV RNA in BAL cells provides a consistent surrogate assessment of virus replication in lung tissue. Innate immune responses contribute to compartmentalized suppression of acute SIV replication in the lungs.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD 21205, USA.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Barber
authors.forename: Lucio
authors.initials: L
authors.lastname: Gama
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Tauni
authors.initials: T
authors.lastname: Voelker
authors.forename: John E
authors.initials: JE
authors.lastname: Anderson
authors.forename: M Christine
authors.initials: MC
authors.lastname: Zink
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Tarwater
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Carruth
authors.forename: Janice E
authors.initials: JE
authors.lastname: Clements
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000276:immunology / Q000821:virology*; D008254:Macaca nemestrina; D016676:Macrophages, Alveolar / Q000821:virology; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral