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

Abstract

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.

Immunopathology of herpes simplex virus‐associated neuroinflammation: Unveiling the mysteries

“…Apparent distinctions in CSF proteomes emerged between HSV‐1, HSV‐2, and varicella‐zoster virus (VZV) samples. Additionally, metabolic pathways linked to cellular and small molecule metabolism were found to be downregulated in cases of HSV‐1 infection 55 . HSV‐1 can potentially induce SANE, a condition marked by heightened neuroinflammation and prolonged neuroimmune activation, posing a life‐threatening scenario.…”

“…Additionally, metabolic pathways linked to cellular and small molecule metabolism were found to be downregulated in cases of HSV-1 infection. 55 HSV-1 can potentially induce SANE, a condition marked by heightened neuroinflammation and prolonged neuroimmune activation, posing a life-threatening scenario. Furthermore, HSV-1 infections within the brain, regardless of symptomatic or asymptomatic presentations, can incite neuronal damage and ultimately contribute to the onset of NDs.…”

Cerebrospinal fluid proteomics in meningitis patients with reactivated varicella zoster virus

“…Studying responses to infections at the proteome level facilitates early diagnosis, risk stratification, and prediction of outcomes, and can help to understand the pathophysiological mechanisms. But to date, few studies have been conducted on CSF proteomics in patients with VZV meningitis 8–12 . In this study, the highly sensitive and reproducible data‐independent acquisition (DIA) based proteomics technology was employed to evaluate the differences in protein levels in CSF of patients with VZV meningitis and HZ, aiming to identify protein markers that are specifically dysregulated in patients with VZV meningitis and to improve our understanding of the pathological mechanism of VZV CNS infection.…”