title: Expression profiles of genes associated with viral entry in HCV-infected human liver.
abstract: Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV-infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL-cholesterol (LDL-C) and HCV core antigen were also evaluated, and expression of claudin-1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin-1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up-regulated in HCV-infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin-1, occludin versus claudin-1, and CD81 versus SR-BI in HCV-infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL-C (P = 0.0147), with their levels negatively correlated to LDLR (P = 0.0270 and P = 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin-1 and occludin was increased in HCV-infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin-1 in HCV-infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV-infected and normal livers.
authors.affiliation: Clinical Research Center, Kyushu Medical Center, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakamuta
authors.forename: T
authors.initials: T
authors.lastname: Fujino
authors.forename: R
authors.initials: R
authors.lastname: Yada
authors.forename: Y
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: K
authors.initials: K
authors.lastname: Yasutake
authors.forename: M
authors.initials: M
authors.lastname: Kohjima
authors.forename: K
authors.initials: K
authors.lastname: Fukuizumi
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Yada
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Kotoh
authors.forename: A
authors.initials: A
authors.lastname: Taketomi
authors.forename: Y
authors.initials: Y
authors.lastname: Maehara
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Enjoji
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D008078:Cholesterol, LDL / Q000097:blood; D062445:Claudin-1; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D062793:Occludin; D011973:Receptors, LDL / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis; D060225:Tetraspanin 28; D014758:Viral Core Proteins / Q000097:blood; D053586:Virus Internalization
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; C568108:CLDN1 protein, human; D008078:Cholesterol, LDL; D062445:Claudin-1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D011973:Receptors, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus