Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection
Infection by Japanese Encephalitis Virus (JEV) in humans is primarily characterized by signs and symptoms including non-specific febrile illness, arthralgia, myalgia etc. followed by its resolution due to joint action of host innate and adaptive immunity. However, in selective cases, complications a...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | IBRO Neuroscience Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242122000847 |
| _version_ | 1811184422375915520 |
|---|---|
| author | Surajit Chakraborty Ellora Sen Anirban Basu |
| author_facet | Surajit Chakraborty Ellora Sen Anirban Basu |
| author_sort | Surajit Chakraborty |
| collection | DOAJ |
| description | Infection by Japanese Encephalitis Virus (JEV) in humans is primarily characterized by signs and symptoms including non-specific febrile illness, arthralgia, myalgia etc. followed by its resolution due to joint action of host innate and adaptive immunity. However, in selective cases, complications arise owing to invasion of central nervous system (CNS) by JEV. Patients being unable to control peripheral viral replication owing to differences in host genetics and immunity experience JEV-associated neurological complications manifested in the form of headache, nausea, meningoencephalitis, coma and eventual death. Entry of JEV into CNS activates complex cascade of events resulting in loss of neuronal physiology and thus CNS tissue integrity. In present study, we have demonstrated role played by JEV in modulation of neuronal pyruvate dehydrogenase kinase 1 (PDK1) abundance and its effect upon neuronal health. Infection of neuron by JEV culminates into upregulation of PDK1 abundance. Albeit inhibition of JEV-induced PDK1-upregulation was accompanied by enhanced JEV propagation in neurons, abrogation of PDK1-upregulation was demonstrated to ameliorate neuronal apoptosis. PDK1 inhibition-associated reduction in neuronal death was observed to be associated with reduced generation of reactive oxygen species (ROS) in neurons. Our study hence provides a possible therapeutic target which upon modulation might help combat JEV infection-associated neuronal apoptosis via restoration of JEV-associated ROS generation. |
| first_indexed | 2024-04-11T13:11:55Z |
| format | Article |
| id | doaj.art-cdbfbfa475bc4add95319ff34c480a2b |
| institution | Directory Open Access Journal |
| issn | 2667-2421 |
| language | English |
| last_indexed | 2024-04-11T13:11:55Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj.art-cdbfbfa475bc4add95319ff34c480a2b2022-12-22T04:22:34ZengElsevierIBRO Neuroscience Reports2667-24212022-12-0113410419Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infectionSurajit Chakraborty0Ellora Sen1Anirban Basu2National Brain Research Centre, Manesar, Haryana, IndiaNational Brain Research Centre, Manesar, Haryana, IndiaCorresponding author.; National Brain Research Centre, Manesar, Haryana, IndiaInfection by Japanese Encephalitis Virus (JEV) in humans is primarily characterized by signs and symptoms including non-specific febrile illness, arthralgia, myalgia etc. followed by its resolution due to joint action of host innate and adaptive immunity. However, in selective cases, complications arise owing to invasion of central nervous system (CNS) by JEV. Patients being unable to control peripheral viral replication owing to differences in host genetics and immunity experience JEV-associated neurological complications manifested in the form of headache, nausea, meningoencephalitis, coma and eventual death. Entry of JEV into CNS activates complex cascade of events resulting in loss of neuronal physiology and thus CNS tissue integrity. In present study, we have demonstrated role played by JEV in modulation of neuronal pyruvate dehydrogenase kinase 1 (PDK1) abundance and its effect upon neuronal health. Infection of neuron by JEV culminates into upregulation of PDK1 abundance. Albeit inhibition of JEV-induced PDK1-upregulation was accompanied by enhanced JEV propagation in neurons, abrogation of PDK1-upregulation was demonstrated to ameliorate neuronal apoptosis. PDK1 inhibition-associated reduction in neuronal death was observed to be associated with reduced generation of reactive oxygen species (ROS) in neurons. Our study hence provides a possible therapeutic target which upon modulation might help combat JEV infection-associated neuronal apoptosis via restoration of JEV-associated ROS generation.http://www.sciencedirect.com/science/article/pii/S2667242122000847 |
| spellingShingle | Surajit Chakraborty Ellora Sen Anirban Basu Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection IBRO Neuroscience Reports |
| title | Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection |
| title_full | Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection |
| title_fullStr | Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection |
| title_full_unstemmed | Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection |
| title_short | Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection |
| title_sort | pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon japanese encephalitis virus infection |
| url | http://www.sciencedirect.com/science/article/pii/S2667242122000847 |
| work_keys_str_mv | AT surajitchakraborty pyruvatedehydrogenasekinase1promotesneuronalapoptosisuponjapaneseencephalitisvirusinfection AT ellorasen pyruvatedehydrogenasekinase1promotesneuronalapoptosisuponjapaneseencephalitisvirusinfection AT anirbanbasu pyruvatedehydrogenasekinase1promotesneuronalapoptosisuponjapaneseencephalitisvirusinfection |