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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...

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Autores principales: Matsuoka, Shelby, Petri, Gloria, Larson, Kristen, Behnke, Alexandra, Wang, Xisheng, Peng, Muhui, Spagnoli, Sean, Lohr, Christiane, Milston-Clements, Ruth, Divilov, Konstantin, Jin, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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