Equal amounts of intracellular and virion-enclosed hepatitis C virus RNA are associated with peripheral-blood mononuclear cells in vivo.
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.
Kaiser
Philipp
P
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 8032 Zurich, Switzerland.
Niederost
Barbara
B
Joos
Beda
B
von Wyl
Viktor
V
Opravil
Milos
M
Weber
Rainer
R
Gunthard
Huldrych F
HF
Fischer
Marek
M
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*
D012367:RNA, Viral