Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: compartmentalized regulation of SIV.
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.
Barber
Sheila A
SA
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD 21205, USA.
Gama
Lucio
L
Li
Ming
M
Voelker
Tauni
T
Anderson
John E
JE
Zink
M Christine
MC
Tarwater
Patrick M
PM
Carruth
Lucy M
LM
Clements
Janice E
JE
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
D004279:DNA, Viral; D012367:RNA, Viral