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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2757 |
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| author | Saima Ahmed Patrick van Zalm Emily A. Rudmann Michael Leone Kiana Keller John A. Branda Judith Steen Shibani S. Mukerji Hanno Steen |
| author_facet | Saima Ahmed Patrick van Zalm Emily A. Rudmann Michael Leone Kiana Keller John A. Branda Judith Steen Shibani S. Mukerji Hanno Steen |
| author_sort | Saima Ahmed |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T15:44:57Z |
| format | Article |
| id | doaj.art-9854b48c7f3d46579357a022b2699a6b |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:44:57Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-9854b48c7f3d46579357a022b2699a6b2023-11-24T18:39:05ZengMDPI AGViruses1999-49152022-12-011412275710.3390/v14122757Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous SystemSaima Ahmed0Patrick van Zalm1Emily A. Rudmann2Michael Leone3Kiana Keller4John A. Branda5Judith Steen6Shibani S. Mukerji7Hanno Steen8Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USANeuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USANeuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USANeuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USANeuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USAHerpesviruses 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.https://www.mdpi.com/1999-4915/14/12/2757liquid chromatography/mass spectrometry (LC/MS)CSF proteomicsherpesvirusbiomarkersCNShuman herpes simplex 1 (HSV-1) |
| spellingShingle | Saima Ahmed Patrick van Zalm Emily A. Rudmann Michael Leone Kiana Keller John A. Branda Judith Steen Shibani S. Mukerji Hanno Steen Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System Viruses liquid chromatography/mass spectrometry (LC/MS) CSF proteomics herpesvirus biomarkers CNS human herpes simplex 1 (HSV-1) |
| 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 | liquid chromatography/mass spectrometry (LC/MS) CSF proteomics herpesvirus biomarkers CNS human herpes simplex 1 (HSV-1) |
| url | https://www.mdpi.com/1999-4915/14/12/2757 |
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