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A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis.
- Source :
-
Scientific reports [Sci Rep] 2021 Sep 21; Vol. 11 (1), pp. 18688. Date of Electronic Publication: 2021 Sep 21. - Publication Year :
- 2021
-
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 (R <superscript>2</superscript> = 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.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Antiviral Agents therapeutic use
Base Sequence
Blood-Brain Barrier
Brain virology
Chlorocebus aethiops
Encephalitis, Herpes Simplex drug therapy
Encephalitis, Herpes Simplex virology
Genes, Reporter
Genes, Viral
Herpesvirus 1, Human genetics
Herpesvirus 1, Human physiology
Luminescence
Mice
Mice, Inbred BALB C
Multiplex Polymerase Chain Reaction methods
Valacyclovir therapeutic use
Vero Cells
Viral Load
Virus Replication genetics
Encephalitis, Herpes Simplex physiopathology
Herpesvirus 1, Human isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 34548521
- Full Text :
- https://doi.org/10.1038/s41598-021-98047-z