Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections
<span style="font-variant: small-caps;">l</span>-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 un...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/8/837 |
| _version_ | 1797716633316229120 |
|---|---|
| author | Efseveia Frakolaki Katerina I. Kalliampakou Panagiota Kaimou Maria Moraiti Nikolaos Kolaitis Haralabia Boleti John Koskinas Dido Vassilacopoulou Niki Vassilaki |
| author_facet | Efseveia Frakolaki Katerina I. Kalliampakou Panagiota Kaimou Maria Moraiti Nikolaos Kolaitis Haralabia Boleti John Koskinas Dido Vassilacopoulou Niki Vassilaki |
| author_sort | Efseveia Frakolaki |
| collection | DOAJ |
| description | <span style="font-variant: small-caps;">l</span>-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 levels in liver biopsies from chronically infected patients. These data reveal a novel relationship between DDC and <i>Flaviviridae</i> replication cycle and the role of PI3K in this process. |
| first_indexed | 2024-03-12T08:24:21Z |
| format | Article |
| id | doaj.art-142f93ae258e4f45a15634887be85455 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:24:21Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-142f93ae258e4f45a15634887be854552023-09-02T18:09:02ZengMDPI AGCells2073-44092019-08-018883710.3390/cells8080837cells8080837Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus InfectionsEfseveia Frakolaki0Katerina I. Kalliampakou1Panagiota Kaimou2Maria Moraiti3Nikolaos Kolaitis4Haralabia Boleti5John Koskinas6Dido Vassilacopoulou7Niki Vassilaki8Laboratory of Molecular Virology, Hellenic Pasteur Institute (HPI), 11521 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute (HPI), 11521 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute (HPI), 11521 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute (HPI), 11521 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute (HPI), 11521 Athens, GreeceLight Microscopy Unit, Hellenic Pasteur Institute, 11521 Athens, Greece2nd Department of Internal Medicine, Medical School of Athens, Hippokration Hospital, 11521 Athens, GreeceSection of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute (HPI), 11521 Athens, Greece<span style="font-variant: small-caps;">l</span>-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 levels in liver biopsies from chronically infected patients. These data reveal a novel relationship between DDC and <i>Flaviviridae</i> replication cycle and the role of PI3K in this process.https://www.mdpi.com/2073-4409/8/8/837hepatitis C virusdengue virus<span style="font-variant: small-caps">l</span>-dopa decarboxylasephosphoinosite-3-kinase (PI3K) |
| spellingShingle | Efseveia Frakolaki Katerina I. Kalliampakou Panagiota Kaimou Maria Moraiti Nikolaos Kolaitis Haralabia Boleti John Koskinas Dido Vassilacopoulou Niki Vassilaki Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections Cells hepatitis C virus dengue virus <span style="font-variant: small-caps ">l</span>-dopa decarboxylase phosphoinosite-3-kinase (PI3K) |
| title | Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections |
| title_full | Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections |
| title_fullStr | Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections |
| title_full_unstemmed | Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections |
| title_short | Emerging Role of <span style="font-variant: small-caps;">l</span>-Dopa Decarboxylase in Flaviviridae Virus Infections |
| title_sort | emerging role of span style font variant small caps l span dopa decarboxylase in flaviviridae virus infections |
| topic | hepatitis C virus dengue virus <span style="font-variant: small-caps ">l</span>-dopa decarboxylase phosphoinosite-3-kinase (PI3K) |
| url | https://www.mdpi.com/2073-4409/8/8/837 |
| work_keys_str_mv | AT efseveiafrakolaki emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT katerinaikalliampakou emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT panagiotakaimou emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT mariamoraiti emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT nikolaoskolaitis emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT haralabiaboleti emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT johnkoskinas emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT didovassilacopoulou emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections AT nikivassilaki emergingroleofspanstylefontvariantsmallcapslspandopadecarboxylaseinflaviviridaevirusinfections |