Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Cells
Efseveia FrakolakiNiki Vassilaki

Abstract

l-dopa decarboxylase (DDC) that catalyzes the biosynthesis of bioactive amines, such as dopamine and serotonin, is expressed in the nervous system and peripheral tissues, including the liver, where its physiological role remains unknown. Recently, we reported a physical and functional interaction of DDC with the major signaling regulator phosphoinosite-3-kinase (PI3K). Here, we provide compelling evidence for the involvement of DDC in viral infections. Studying dengue (DENV) and hepatitis C (HCV) virus infection in hepatocytes and HCV replication in liver samples of infected patients, we observed a negative association between DDC and viral replication. Specifically, replication of both viruses reduced the levels of DDC mRNA and the ~120 kDa SDS-resistant DDC immunoreactive functional complex, concomitant with a PI3K-dependent accumulation of the ~50 kDa DDC monomer. Moreover, viral infection inhibited PI3K-DDC association, while DDC did not colocalize with viral replication sites. DDC overexpression suppressed DENV and HCV RNA replication, while DDC enzymatic inhibition enhanced viral replication and infectivity and affected DENV-induced cell death. Consistently, we observed an inverse correlation between DDC mRNA and HCV RNA ...Continue Reading

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Methods Mentioned

BETA
Biopsy
in vitro transcription
Infection
Electrophoresis
Immunoprecipitation
PCR
co-immunoprecipitation assay
transfection
biopsies
co-immunoprecipitation

Software Mentioned

Prism
Excel
Quantity I
GraphPad
Icy
Colocalization Studio

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