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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-03-0818.

Submitted March 18, 2002
Accepted June 12, 2002
Differential distribution and internal translation efficiency of hepatitis C virus quasispecies present in dendritic and liver cells
Julien Laporte, Christine Bain, Patrick Maurel, Genevieve Inchauspe, Henri Agut, and Annie Cahour*
Laboratoire de virologie, CERVI, UPRES EA 2387, Hopital Pitie-Salpetriere, Paris, France
Unite Mixte CNRS-bioMerieux, Ecole Normale Superieure, Lyon, France
CNRS, BP5051, INSERM Unite 128, Montpellier, France
* Corresponding author; email: cahour{at}idf.ext.jussieu.fr.
Hepatitis C virus (HCV) is predominantly a hepatotropic virus. Nonetheless, there is a mounting evidence that hematopoietic cells may support HCV replication. The HCV 5' untranslated region (5'UTR), responsible for initiation of viral translation, via an internal ribosome entry site (IRES), has been previously described to contain specific nucleotide substitutions when cultured in infected lymphoid cells. Our purpose was to establish whether the 5'UTR polymorphism of quasispecies from three cell compartments (monocyte-derived dendritic cells [DC], PBMC and liver) of a patient chronically-infected with HCV 1b affects the corresponding translational efficiencies and thus the capacity for replication. 5'UTR polymorphism was characterized by identification of changes at three crucial sites as compared to the reference nucleotide (nt) sequence: a G insertion between positions 19 and 20, a C to A substitution at position 204 and a G to A substitution at position 243. The quasispecies detected in DC was unique and differed from those present in the liver, suggesting a particular tropism of HCV quasispecies for DC. Moreover, its translational activity was significantly impaired when compared with those from liver and PBMC in different cell lines. This impairment was thoroughly confirmed in primary cultures of both human hepatocytes and monocyte-derived DC. Taken together, our data lend support both to a specific location and impaired replication of HCV quasispecies in DC, which could be related to viral persistence and perturbation of DC function in chronically-infected patients.

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