Low density lipoprotein receptor transcripts correlates with liver hepatitis C virus RNA in patients with alcohol consumption.
Alcohol consumption has a major impact on the natural history of chronic hepatitis C virus (HCV) infection, although the underlying mechanisms are still debated. We designed a clinical study to evaluate the impact of alcohol abuse on both viral load and expression of low-density lipoprotein receptor (LDLR) and CD81 expression. Thirty-eight consecutive HCV-infected patients were enrolled. Group 1 (n = 18), < or =10 g alcohol/day, group 2 (n = 8), < or =30 g alcohol/day, group 3 (n = 12), >or =30 g alcohol/day. Receptors expression was measured by flow cytometry analysis in peripheral blood mononuclear cells (PBMC) and by specific real-time retrotranscription polymerase chain reaction (RT-PCR) in the liver. Serum viral load was evaluated by quantification of both HCV genomic RNA and total core antigen. The hepatic viral load was assessed by real-time RT-PCR. Serum HCV-RNA and total core antigen were significantly correlated, and were higher, albeit not significantly, in group 3 than in group 1. Alcohol consumption had no effect on expression of HCV putative receptors in PBMC, except for CD81, which was upregulated on monocytes in group 2. In the liver, viral load and levels of LDLR transcripts were significantly higher in group 3 than in group 1. Remarkably, a significant positive correlation was found between LDLR transcripts and HCV-RNA (r2 = 0.83, P < 10(-3)). Finally, in vitro experiments suggested that the effect of ethanol on LDLR expression was indirectly mediated by both tumour necrosis factor-alpha and interleukin-1beta. In conclusion, this study is the first to support a role for LDLR in the natural infection by HCV in man.
Carrière
M
M
UPRESS 1833, Faculté de Médecine Paris V, France.
Rosenberg
A R
AR
Conti
F
F
Chouzenoux
S
S
Terris
B
B
Sogni
P
P
Soubrane
O
O
Calmus
Y
Y
Podevin
P
P
D000328:Adult; D000428:Alcohol Drinking; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008099:Liver / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood; D011973:Receptors, LDL / Q000096:biosynthesis / Q000235:genetics*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic; D060225:Tetraspanin 28; D014158:Transcription, Genetic; D019562:Viral Load
D015703:Antigens, CD; C554798:CD81 protein, human; D012367:RNA, Viral; D011973:Receptors, LDL; D011991:Receptors, Virus; D060225:Tetraspanin 28