Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.3.2.19 (
ubiquitin-protein ligase
)
799
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
HCV infection can decrease NAD
+
/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes,
quinolinate phosphoribosyl transferase
(
QPRT
) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates
QPRT
hence the lipogenesis is unknown. In this work, we found
QPRT
was reduced significantly in livers of patients or humanized C/O
Tg
mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of
QPRT
through Smurf2, an E3
ubiquitin-protein ligase
, in Huh7.5.1 cells. Furthermore,
QPRT
enzymatic activity involved in suppression of HCV replication in cells. Activation of
QPRT
with clofibrate (CLO) or addition of
QPRT
catabolite NAD both inhibited HCV replication in cells, probably through NAD
+
-dependent Sirt1 inhibition of cellular lipogenesis. More importantly, administration of CLO, a hypolipidemic drug used in clinics, could significantly reduce the viral load in HCV infected C/O
Tg
mice. Take together, these results suggested that HCV infection triggered proteasomal degradation of
QPRT
and consequently reduced de novo NAD synthesis and lipogenesis, in favor of HCV replication. Hepatic
QPRT
thus likely served as a cellular factor that dampened productive HCV replication.
...
PMID:Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection. 2872 15
