Using CSF Proteomics to Investigate Herpesvirus Infections of the Central Nervous System
Saima Ahmed,
Patrick van Zalm,
Emily A. Rudmann,
Michael Leone,
Kiana Keller,
John A. Branda,
Judith Steen,
Shibani S. Mukerji,
Hanno Steen
Affiliations
Saima Ahmed
Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Patrick van Zalm
Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Emily A. Rudmann
Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Michael Leone
Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Kiana Keller
Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
John A. Branda
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Judith Steen
F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Shibani S. Mukerji
Neuroimmunology and Neuro-Infectious Diseases Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Hanno Steen
Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
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.
