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Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection
Cyprinid herpesvirus 3 (CyHV-3) can cause severe disease in koi and common carp (Cyprinus carpio). Currently, no effective treatment is available against CyHV-3 infection in koi. Both LSD1 and JMJD2 are histone demethylases (HD) and are critical for immediate-early (IE) gene activation essential for...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863241/ https://www.ncbi.nlm.nih.gov/pubmed/36680202 http://dx.doi.org/10.3390/v15010163 |
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author | Matsuoka, Shelby Petri, Gloria Larson, Kristen Behnke, Alexandra Wang, Xisheng Peng, Muhui Spagnoli, Sean Lohr, Christiane Milston-Clements, Ruth Divilov, Konstantin Jin, Ling |
author_facet | Matsuoka, Shelby Petri, Gloria Larson, Kristen Behnke, Alexandra Wang, Xisheng Peng, Muhui Spagnoli, Sean Lohr, Christiane Milston-Clements, Ruth Divilov, Konstantin Jin, Ling |
author_sort | Matsuoka, Shelby |
collection | PubMed |
description | Cyprinid herpesvirus 3 (CyHV-3) can cause severe disease in koi and common carp (Cyprinus carpio). Currently, no effective treatment is available against CyHV-3 infection in koi. Both LSD1 and JMJD2 are histone demethylases (HD) and are critical for immediate-early (IE) gene activation essential for lytic herpesvirus replication. OG-L002 and ML324 are newly discovered specific inhibitors of LSD1 and JMJD2, respectively. Here, HD inhibitors were compared with acyclovir (ACV) against CyHV-3 infection in vitro and in vivo. ML324, at 20–50 µM, can completely block ~1 × 10(3) PFU CyHV-3 replication in vitro, while OG-L002 at 20 µM and 50 µM can produce 96% and 98% inhibition, respectively. Only about 94% inhibition of ~1 × 10(3) PFU CyHV-3 replication was observed in cells treated with ACV at 50 µM. As expected, CyHV-3 IE gene transcription of ORF139 and ORF155 was blocked within 72 h post-infection (hpi) in the presence of 20 µM ML324. No detectable cytotoxicity was observed in KF-1 or CCB cells treated for 24 h with 1 to 50 µM ML324. A significant reduction of CyHV-3 replication was observed in ~6-month-old infected koi treated with 20 µM ML324 in an immersion bath for 3–4 h at 1-, 3-, and 5-days post-infection compared to the control and ACV treatments. Under heat stress, 50–70% of 3–4-month-old koi survived CyHV-3 infection when they were treated daily with 20 µM ML324 in an immersion bath for 3–4 h within the first 5 d post-infection (dpi), compared to 11–19% and 22–27% of koi in the control and ACV treatments, respectively. Our study demonstrates that ML324 has the potential to be used against CyHV-3 infection in koi. |
format | Online Article Text |
id | pubmed-9863241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98632412023-01-22 Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection Matsuoka, Shelby Petri, Gloria Larson, Kristen Behnke, Alexandra Wang, Xisheng Peng, Muhui Spagnoli, Sean Lohr, Christiane Milston-Clements, Ruth Divilov, Konstantin Jin, Ling Viruses Article Cyprinid herpesvirus 3 (CyHV-3) can cause severe disease in koi and common carp (Cyprinus carpio). Currently, no effective treatment is available against CyHV-3 infection in koi. Both LSD1 and JMJD2 are histone demethylases (HD) and are critical for immediate-early (IE) gene activation essential for lytic herpesvirus replication. OG-L002 and ML324 are newly discovered specific inhibitors of LSD1 and JMJD2, respectively. Here, HD inhibitors were compared with acyclovir (ACV) against CyHV-3 infection in vitro and in vivo. ML324, at 20–50 µM, can completely block ~1 × 10(3) PFU CyHV-3 replication in vitro, while OG-L002 at 20 µM and 50 µM can produce 96% and 98% inhibition, respectively. Only about 94% inhibition of ~1 × 10(3) PFU CyHV-3 replication was observed in cells treated with ACV at 50 µM. As expected, CyHV-3 IE gene transcription of ORF139 and ORF155 was blocked within 72 h post-infection (hpi) in the presence of 20 µM ML324. No detectable cytotoxicity was observed in KF-1 or CCB cells treated for 24 h with 1 to 50 µM ML324. A significant reduction of CyHV-3 replication was observed in ~6-month-old infected koi treated with 20 µM ML324 in an immersion bath for 3–4 h at 1-, 3-, and 5-days post-infection compared to the control and ACV treatments. Under heat stress, 50–70% of 3–4-month-old koi survived CyHV-3 infection when they were treated daily with 20 µM ML324 in an immersion bath for 3–4 h within the first 5 d post-infection (dpi), compared to 11–19% and 22–27% of koi in the control and ACV treatments, respectively. Our study demonstrates that ML324 has the potential to be used against CyHV-3 infection in koi. MDPI 2023-01-05 /pmc/articles/PMC9863241/ /pubmed/36680202 http://dx.doi.org/10.3390/v15010163 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matsuoka, Shelby Petri, Gloria Larson, Kristen Behnke, Alexandra Wang, Xisheng Peng, Muhui Spagnoli, Sean Lohr, Christiane Milston-Clements, Ruth Divilov, Konstantin Jin, Ling Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection |
title | Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection |
title_full | Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection |
title_fullStr | Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection |
title_full_unstemmed | Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection |
title_short | Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection |
title_sort | evaluation of histone demethylase inhibitor ml324 and acyclovir against cyprinid herpesvirus 3 infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863241/ https://www.ncbi.nlm.nih.gov/pubmed/36680202 http://dx.doi.org/10.3390/v15010163 |
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