Serum-derived hepatitis C virus infection of primary human hepatocytes is tetraspanin CD81 dependent.
Hepatitis C virus-positive serum (HCVser, genotypes 1a to 3a) or HCV cell culture (JFH1/HCVcc) infection of primary normal human hepatocytes was assessed by measuring intracellular HCV RNA strands. Anti-CD81 antibodies and siRNA-CD81 silencing markedly inhibited (>90%) HCVser infection irrespective of HCV genotype, viral load, or liver donor, while hCD81-large intracellular loop (LEL) had no effect. However, JFH1/HCVcc infection of hepatocytes was modestly inhibited (40 to 60%) by both hCD81-LEL and anti-CD81 antibodies. In conclusion, CD81 is involved in HCVser infection of human hepatocytes, and comparative studies of HCVser versus JFH1/HCVcc infection of human hepatocytes and Huh-7.5 cells revealed that the cell-virion combination is determinant of the entry process.
Molina
Sonia
S
Inserm U632, Hepatic Physiopathology, 1919 route de Mende, 34293 Montpellier, Cedex 5, France.
Castet
Valerie
V
Pichard-Garcia
Lydiane
L
Wychowski
Czeslaw
C
Meurs
Eliane
E
Pascussi
Jean-Marc
JM
Sureau
Camille
C
Fabre
Jean-Michel
JM
Sacunha
Antonio
A
Larrey
Dominique
D
Dubuisson
Jean
J
Coste
Joliette
J
McKeating
Jane
J
Maurel
Patrick
P
Fournier-Wirth
Chantal
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000737:chemistry / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D060225:Tetraspanin 28; D053586:Virus Internalization
D015703:Antigens, CD; C554798:CD81 protein, human; D012367:RNA, Viral; D011991:Receptors, Virus; D060225:Tetraspanin 28