Evidence of viral replication in circulating dendritic cells during hepatitis C virus infection.
The existence of extrahepatic sites of hepatitis C virus (HCV) replication has been proposed as a mechanism responsible for the poor antiviral immune response found in chronic infection. Dendritic cells (DCs), as unique antigen-presenting cells able to induce a primary immune response, are prime targets of persistent viruses. From 24 blood samples obtained from HCV-seropositive patients, peripheral blood DCs (PBDCs) were purified. HCV genomic sequences were specifically detected by reverse-transcription polymerase chain reaction in 6 of 24 PBDC pellets, and replicative-strand RNA also was found in 3 of 24 cell purifications. Analysis of the HCV quasi-species distribution in the PBDC population of 1 patient showed the presence of a dominant variant different from that found in plasma with respect to the primary amino-acid sequence and physicochemical profile of the hypervariable region 1 of glycoprotein E2. These data strongly suggest that PBDCs constitute a reservoir in which HCV replication takes place during natural infection.
Goutagny
Nadège
N
Unité Mixte de Recherche 2142, Centre National de la Recherche Scientifique Biomérieux, Lyon, France.
Fatmi
Ahmed
A
De Ledinghen
Victor
V
Penin
François
F
Couzigou
Patrice
P
Inchauspé
Geneviève
G
Bain
Christine
C
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D003713:Dendritic Cells / Q000821:virology*; D005260:Female; D005814:Genes, Viral; D016679:Genome, Viral; D016174:Hepacivirus / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013045:Species Specificity; D014779:Virus Replication