Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection
We reported that gamma-hydroxybutyrate (GHB) is released upon Herpes Simplex Virus Type-1 (HSV-1) acute infection. However, the cellular biochemical processes involved in the production of GHB in infected cells are unclear. This study aims to shed light on the biochemical pathway and the stage withi...
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MDPI AG
2023-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/8/1104 |
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| author | Faith O. Osinaga Yu-Chih Chen Madan K. Kharel Yan Waguespack Sichu Li Shaochung Victor Hsia |
| author_facet | Faith O. Osinaga Yu-Chih Chen Madan K. Kharel Yan Waguespack Sichu Li Shaochung Victor Hsia |
| author_sort | Faith O. Osinaga |
| collection | DOAJ |
| description | We reported that gamma-hydroxybutyrate (GHB) is released upon Herpes Simplex Virus Type-1 (HSV-1) acute infection. However, the cellular biochemical processes involved in the production of GHB in infected cells are unclear. This study aims to shed light on the biochemical pathway and the stage within the viral life cycle responsible for the release of GHB in infected cells. UV-inactivation, acyclovir (ACV), and cycloheximide (CHX) treatments were used to inhibit HSV-1 replication at various stages. Vero cells treated with UV-inactivated HSV-1 significantly decreased GHB production. However, ACV or CHX treatments did not affect GHB production. We also showed that inhibition of glycolytic enzyme enolase by sodium fluoride (NaF) significantly reduces GHB production upon infection. This finding suggests that suppression of glycolytic activity negatively affects cellular GHB production. Our data also indicated that succinic semialdehyde dehydrogenase, an enzyme involved in the shunt of the tricarboxylic acid (TCA) cycle to generate succinic acid, was decreased upon infection, suggesting that infection may trigger the accumulation of succinic semialdehyde, causing the production of GHB. Although the precise mechanism has yet to be defined, our results suggest that early events following infection modulates the release of GHB, which is generated through the metabolic pathways of glycolysis and TCA cycle. |
| first_indexed | 2024-03-10T23:39:40Z |
| format | Article |
| id | doaj.art-88f2124cc116411585a51b91479f7330 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T23:39:40Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-88f2124cc116411585a51b91479f73302023-11-19T02:33:59ZengMDPI AGPharmaceuticals1424-82472023-08-01168110410.3390/ph16081104Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute InfectionFaith O. Osinaga0Yu-Chih Chen1Madan K. Kharel2Yan Waguespack3Sichu Li4Shaochung Victor Hsia5Department of Pharmaceutical Science, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USADepartment of Pharmaceutical Science, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USADepartment of Pharmaceutical Science, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USADepartment of Natural Science, School of Agriculture and Natural Science, University of Maryland Eastern Shore, Princess Anne, MD 21853, USAKnowledge Bridge, LLC, Fairfax, VA 22032, USADepartment of Pharmaceutical Science, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USAWe reported that gamma-hydroxybutyrate (GHB) is released upon Herpes Simplex Virus Type-1 (HSV-1) acute infection. However, the cellular biochemical processes involved in the production of GHB in infected cells are unclear. This study aims to shed light on the biochemical pathway and the stage within the viral life cycle responsible for the release of GHB in infected cells. UV-inactivation, acyclovir (ACV), and cycloheximide (CHX) treatments were used to inhibit HSV-1 replication at various stages. Vero cells treated with UV-inactivated HSV-1 significantly decreased GHB production. However, ACV or CHX treatments did not affect GHB production. We also showed that inhibition of glycolytic enzyme enolase by sodium fluoride (NaF) significantly reduces GHB production upon infection. This finding suggests that suppression of glycolytic activity negatively affects cellular GHB production. Our data also indicated that succinic semialdehyde dehydrogenase, an enzyme involved in the shunt of the tricarboxylic acid (TCA) cycle to generate succinic acid, was decreased upon infection, suggesting that infection may trigger the accumulation of succinic semialdehyde, causing the production of GHB. Although the precise mechanism has yet to be defined, our results suggest that early events following infection modulates the release of GHB, which is generated through the metabolic pathways of glycolysis and TCA cycle.https://www.mdpi.com/1424-8247/16/8/1104gamma-hydroxybutyrateUPLC-MRM-MSvirologymass spectrometry |
| spellingShingle | Faith O. Osinaga Yu-Chih Chen Madan K. Kharel Yan Waguespack Sichu Li Shaochung Victor Hsia Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection Pharmaceuticals gamma-hydroxybutyrate UPLC-MRM-MS virology mass spectrometry |
| title | Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection |
| title_full | Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection |
| title_fullStr | Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection |
| title_full_unstemmed | Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection |
| title_short | Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection |
| title_sort | early events after herpes simplex virus type 1 entry are necessary for the release of gamma hydroxybutyrate upon acute infection |
| topic | gamma-hydroxybutyrate UPLC-MRM-MS virology mass spectrometry |
| url | https://www.mdpi.com/1424-8247/16/8/1104 |
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