{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:38:20Z","timestamp":1781534300236,"version":"3.54.5"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:00:00Z","timestamp":1670630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"the National Institute of Mental Health at the National Institutes of Health","doi-asserted-by":"publisher","award":["K23MH115812"],"award-info":[{"award-number":["K23MH115812"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"the National Institute of Mental Health at the National Institutes of Health","doi-asserted-by":"publisher","award":["5U24AI152179-02"],"award-info":[{"award-number":["5U24AI152179-02"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"name":"James S. McDonnell Foundation","award":["K23MH115812"],"award-info":[{"award-number":["K23MH115812"]}]},{"name":"James S. McDonnell Foundation","award":["5U24AI152179-02"],"award-info":[{"award-number":["5U24AI152179-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v14122757","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T03:36:09Z","timestamp":1670816169000},"page":"2757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-036X","authenticated-orcid":false,"given":"Saima","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"van Zalm","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Rudmann","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leone","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana","family":"Keller","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Branda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Steen","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5677-6954","authenticated-orcid":false,"given":"Shibani S.","family":"Mukerji","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0179-6648","authenticated-orcid":false,"given":"Hanno","family":"Steen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Precision Vaccines Program and Neurobiology Program, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/ncpneuro0401","article-title":"Herpesvirus infections of the nervous system","volume":"3","author":"Gilden","year":"2007","journal-title":"Nat. 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