Hepatitis C virus enters human peripheral neuroblastoma cells - evidence for extra-hepatic cells sustaining hepatitis C virus penetration.
Patients with chronic hepatitis C virus (HCV) infection show an increased incidence of nervous system disorders such as chronic fatigue syndrome, depression and cognitive dysfunction. It is unclear whether this is because of HCV replication in the brain and in peripheral neuronal cells or to more indirect effects of HCV infection on the central or peripheral nervous system. The aim of this study was to investigate whether cells originating from these tissues are permissive for HCV cell entry, RNA replication and virus assembly. Among eight cell lines analysed, the human peripheral neuroblastoma cell line SKNMC expressed all HCV entry factors and was efficiently infected with HCV pseudoparticles (HCVpp) independent of the HCV genotype. All remaining cell types including human neuroblastoma and glioblastoma cell lines and microglial cells lacked expression of at least one host factor essential for HCV entry. When transfected with HCV luciferase reporter virus RNA, inoculated with HCV reporter viruses or challenged with high-titre cell culture-derived HCV, none of these cells supported detectable HCV RNA replication. Thus, in conclusion, this comprehensive screening did not reveal evidence directly strengthening the notion that HCV enters and replicates in the central nervous system. However, productive viral entry into the peripheral neuroblastoma cell line SKNMC indicates that HCV may penetrate into certain nonhepatic cell types which may serve as viral reservoirs and could modulate viral pathogenesis.
Bürgel
B
B
Division of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH) and Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Friesland
M
M
Koch
A
A
Manns
M P
MP
Wedemeyer
H
H
Weissenborn
K
K
Schulz-Schaeffer
W J
WJ
Pietschmann
T
T
Steinmann
E
E
Ciesek
S
S
D015703:Antigens, CD / Q000032:analysis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D062445:Claudin-1; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D017930:Genes, Reporter; D005822:Genetic Vectors; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008156:Luciferases; D008565:Membrane Proteins / Q000032:analysis; D062793:Occludin; D012367:RNA, Viral / Q000032:analysis; D051122:Scavenger Receptors, Class B / Q000032:analysis; D060225:Tetraspanin 28; D014162:Transfection; D053586:Virus Internalization; D014779:Virus Replication
D015703:Antigens, CD; C554798:CD81 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D012367:RNA, Viral; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D008156:Luciferases