A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

Abstract Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herei...

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Autores principales:	Olus Uyar, Pier-Luc Plante, Jocelyne Piret, Marie-Christine Venable, Julie Carbonneau, Jacques Corbeil, Guy Boivin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa32d81874b94e47b48bcca576dc80a1
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spelling	oai:doaj.org-article:aa32d81874b94e47b48bcca576dc80a12021-12-02T18:14:22ZA novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis10.1038/s41598-021-98047-z2045-2322https://doaj.org/article/aa32d81874b94e47b48bcca576dc80a12021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98047-zhttps://doaj.org/toc/2045-2322Abstract Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.Olus UyarPier-Luc PlanteJocelyne PiretMarie-Christine VenableJulie CarbonneauJacques CorbeilGuy BoivinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olus Uyar Pier-Luc Plante Jocelyne Piret Marie-Christine Venable Julie Carbonneau Jacques Corbeil Guy Boivin A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
description	Abstract Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.
format	article
author	Olus Uyar Pier-Luc Plante Jocelyne Piret Marie-Christine Venable Julie Carbonneau Jacques Corbeil Guy Boivin
author_facet	Olus Uyar Pier-Luc Plante Jocelyne Piret Marie-Christine Venable Julie Carbonneau Jacques Corbeil Guy Boivin
author_sort	Olus Uyar
title	A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
title_short	A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
title_full	A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
title_fullStr	A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
title_full_unstemmed	A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
title_sort	novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aa32d81874b94e47b48bcca576dc80a1
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A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

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