Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication
Flaviviruses are relevant animal and human pathogens that include West Nile virus (WNV), Japanese encephalitis virus, dengue virus, or Zika virus, among others. Currently, no licensed therapy is available to fight flaviviral infections. Protein kinases C (PKCs) constitute a family of multifunctional...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-02-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/10/2/91 |
| _version_ | 1819241480846311424 |
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| author | Ana B. Blázquez Ángela Vázquez-Calvo Miguel A. Martín-Acebes Juan-Carlos Saiz |
| author_facet | Ana B. Blázquez Ángela Vázquez-Calvo Miguel A. Martín-Acebes Juan-Carlos Saiz |
| author_sort | Ana B. Blázquez |
| collection | DOAJ |
| description | Flaviviruses are relevant animal and human pathogens that include West Nile virus (WNV), Japanese encephalitis virus, dengue virus, or Zika virus, among others. Currently, no licensed therapy is available to fight flaviviral infections. Protein kinases C (PKCs) constitute a family of multifunctional lipid-dependent isoenzymes that regulate a wide variety of cellular processes (apoptosis, differentiation, proliferation, cellular transformation, motility, adhesion, etc.) being currently considered at the front line of drug development for the treatment of diverse human disorders. PKCs have also been implicated in different steps during viral replication; however, nowadays, results regarding their role in flavivirus replication are controversial. Here we demonstrate that calphostin C and chelerythrine, two broad-PKC inhibitors that target conventional, novel and atypical PKCs, significantly inhibit WNV multiplication in cell culture without affecting cell viability. A reduction of viral yields was observed in treated cells when compared with mock-treated cells. Likewise, immunofluorescence detection of viral enveloped E protein was reduced in treated cells, as was the amount of viral RNA released to the supernatant, mainly in those treated with chelerythrine. On the other hand, two PKC inhibitors specific for conventional and novel isoforms (staurosporine and enzastaurine) did not show any significant effect in WNV multiplication. These results suggested that PKCs, more probably atypical PKCs, are likely involved in WNV multiplication, although both broad-spectrum tested drugs seem to act through different mechanisms, and point to them as potential antiviral candidates for WNV, as well as for other related flaviviruses. |
| first_indexed | 2024-12-23T14:24:35Z |
| format | Article |
| id | doaj.art-dbf1740bf476412f95fdfebe13cb6c21 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-23T14:24:35Z |
| publishDate | 2018-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-dbf1740bf476412f95fdfebe13cb6c212022-12-21T17:43:43ZengMDPI AGViruses1999-49152018-02-011029110.3390/v10020091v10020091Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus ReplicationAna B. Blázquez0Ángela Vázquez-Calvo1Miguel A. Martín-Acebes2Juan-Carlos Saiz3Department of Biotechnology, INIA, Ctra. Coruña Km. 7.5, 28040 Madrid, SpainDepartment of Biotechnology, INIA, Ctra. Coruña Km. 7.5, 28040 Madrid, SpainDepartment of Biotechnology, INIA, Ctra. Coruña Km. 7.5, 28040 Madrid, SpainDepartment of Biotechnology, INIA, Ctra. Coruña Km. 7.5, 28040 Madrid, SpainFlaviviruses are relevant animal and human pathogens that include West Nile virus (WNV), Japanese encephalitis virus, dengue virus, or Zika virus, among others. Currently, no licensed therapy is available to fight flaviviral infections. Protein kinases C (PKCs) constitute a family of multifunctional lipid-dependent isoenzymes that regulate a wide variety of cellular processes (apoptosis, differentiation, proliferation, cellular transformation, motility, adhesion, etc.) being currently considered at the front line of drug development for the treatment of diverse human disorders. PKCs have also been implicated in different steps during viral replication; however, nowadays, results regarding their role in flavivirus replication are controversial. Here we demonstrate that calphostin C and chelerythrine, two broad-PKC inhibitors that target conventional, novel and atypical PKCs, significantly inhibit WNV multiplication in cell culture without affecting cell viability. A reduction of viral yields was observed in treated cells when compared with mock-treated cells. Likewise, immunofluorescence detection of viral enveloped E protein was reduced in treated cells, as was the amount of viral RNA released to the supernatant, mainly in those treated with chelerythrine. On the other hand, two PKC inhibitors specific for conventional and novel isoforms (staurosporine and enzastaurine) did not show any significant effect in WNV multiplication. These results suggested that PKCs, more probably atypical PKCs, are likely involved in WNV multiplication, although both broad-spectrum tested drugs seem to act through different mechanisms, and point to them as potential antiviral candidates for WNV, as well as for other related flaviviruses.http://www.mdpi.com/1999-4915/10/2/91West Nile virusviral replicationprotein kinase C |
| spellingShingle | Ana B. Blázquez Ángela Vázquez-Calvo Miguel A. Martín-Acebes Juan-Carlos Saiz Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication Viruses West Nile virus viral replication protein kinase C |
| title | Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication |
| title_full | Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication |
| title_fullStr | Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication |
| title_full_unstemmed | Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication |
| title_short | Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication |
| title_sort | pharmacological inhibition of protein kinase c reduces west nile virus replication |
| topic | West Nile virus viral replication protein kinase C |
| url | http://www.mdpi.com/1999-4915/10/2/91 |
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