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Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System

Herpesviruses have complex mechanisms enabling infection of the human CNS and evasion of the immune system, allowing for indefinite latency in the host. Herpesvirus infections can cause severe complications of the central nervous system (CNS). Here, we provide a novel characterization of cerebrospin...

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Autores principales: Ahmed, Saima, van Zalm, Patrick, Rudmann, Emily A., Leone, Michael, Keller, Kiana, Branda, John A., Steen, Judith, Mukerji, Shibani S., Steen, Hanno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780940/
https://www.ncbi.nlm.nih.gov/pubmed/36560759
http://dx.doi.org/10.3390/v14122757
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author Ahmed, Saima
van Zalm, Patrick
Rudmann, Emily A.
Leone, Michael
Keller, Kiana
Branda, John A.
Steen, Judith
Mukerji, Shibani S.
Steen, Hanno
author_facet Ahmed, Saima
van Zalm, Patrick
Rudmann, Emily A.
Leone, Michael
Keller, Kiana
Branda, John A.
Steen, Judith
Mukerji, Shibani S.
Steen, Hanno
author_sort Ahmed, Saima
collection PubMed
description Herpesviruses have complex mechanisms enabling infection of the human CNS and evasion of the immune system, allowing for indefinite latency in the host. Herpesvirus infections can cause severe complications of the central nervous system (CNS). Here, we provide a novel characterization of cerebrospinal fluid (CSF) proteomes from patients with meningitis or encephalitis caused by human herpes simplex virus 1 (HSV-1), which is the most prevalent human herpesvirus associated with the most severe morbidity. The CSF proteome was compared with those from patients with meningitis or encephalitis due to human herpes simplex virus 2 (HSV-2) or varicella-zoster virus (VZV, also known as human herpesvirus 3) infections. Virus-specific differences in CSF proteomes, most notably elevated 14-3-3 family proteins and calprotectin (i.e., S100-A8 and S100-A9), were observed in HSV-1 compared to HSV-2 and VZV samples, while metabolic pathways related to cellular and small molecule metabolism were downregulated in HSV-1 infection. Our analyses show the feasibility of developing CNS proteomic signatures of the host response in alpha herpes infections, which is paramount for targeted studies investigating the pathophysiology driving virus-associated neurological disorders, developing biomarkers of morbidity, and generating personalized therapeutic strategies.
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spelling pubmed-97809402022-12-24 Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System Ahmed, Saima van Zalm, Patrick Rudmann, Emily A. Leone, Michael Keller, Kiana Branda, John A. Steen, Judith Mukerji, Shibani S. Steen, Hanno Viruses Article Herpesviruses have complex mechanisms enabling infection of the human CNS and evasion of the immune system, allowing for indefinite latency in the host. Herpesvirus infections can cause severe complications of the central nervous system (CNS). Here, we provide a novel characterization of cerebrospinal fluid (CSF) proteomes from patients with meningitis or encephalitis caused by human herpes simplex virus 1 (HSV-1), which is the most prevalent human herpesvirus associated with the most severe morbidity. The CSF proteome was compared with those from patients with meningitis or encephalitis due to human herpes simplex virus 2 (HSV-2) or varicella-zoster virus (VZV, also known as human herpesvirus 3) infections. Virus-specific differences in CSF proteomes, most notably elevated 14-3-3 family proteins and calprotectin (i.e., S100-A8 and S100-A9), were observed in HSV-1 compared to HSV-2 and VZV samples, while metabolic pathways related to cellular and small molecule metabolism were downregulated in HSV-1 infection. Our analyses show the feasibility of developing CNS proteomic signatures of the host response in alpha herpes infections, which is paramount for targeted studies investigating the pathophysiology driving virus-associated neurological disorders, developing biomarkers of morbidity, and generating personalized therapeutic strategies. MDPI 2022-12-10 /pmc/articles/PMC9780940/ /pubmed/36560759 http://dx.doi.org/10.3390/v14122757 Text en © 2022 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
Ahmed, Saima
van Zalm, Patrick
Rudmann, Emily A.
Leone, Michael
Keller, Kiana
Branda, John A.
Steen, Judith
Mukerji, Shibani S.
Steen, Hanno
Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
title Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
title_full Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
title_fullStr Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
title_full_unstemmed Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
title_short Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
title_sort using csf proteomics to investigate herpesvirus infections of the central nervous system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780940/
https://www.ncbi.nlm.nih.gov/pubmed/36560759
http://dx.doi.org/10.3390/v14122757
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