Reaction of complement factors and proteasomes in experimental encephalitis

Stefan Lange,Ivar Lönnroth,Ewa Johansson,Tomas Bergström,Merna Oshalim

doi:10.1007/s13365-016-0500-1

Abstract

Herpes simplex virus type 1 (HSV-1) encephalitis causes a deleterious inflammation and elevated intracranial pressure. As a step towards examining the origin of the inflammation, we here report the response of circulating proteasomes and complement factors in blood and cerebrospinal fluid (CSF) in rats infected with HSV-1. Infection was via the nasal route, with 1.1 × 104 plaque-forming units of HSV-1 strain 2762 given in one or both nostrils. A sandwich enzyme-linked immunosorbent assay was used to study the level of 26S proteasomes and their complex formation with complement factors 3 and 4. HSV-1 infection in the rat causes a complex formation between complement factors and proteasomes, which we designate compleasomes. In the first experiment, with HSV-1 given in both nostrils, compleasomes containing complement factors 3 and 4 increased significantly in both blood plasma and CSF. The concentration of proteasomes in plasma was similar in controls and infected rats (320 ± 163 vs. 333 ± 125 ng/ml). In the second experiment, with HSV-1 given in one nostril, CSF levels were 1 ± 1 ng/ml in controls and 56 ± 22 ng/ml in the HSV-1 group, whereas the total protein concentration in CSF remained the same in the two groups. The compleasome response was limited to CSF, with a highly significant difference between infected rats and controls (n = 11, p < 0.001). It was possible to mimic the reaction between proteasomes and complements 3 and 4 in vitro in the presence of ATP.

Highlights

Herpes simplex virus type 1 (HSV-1), a usually benign virus that commonly causes recurrent oral lesions, may occasionally induce a necrotizing encephalitis focused on the frontotemporal regions of the brain
We have previously shown that a peptide derived from the proteasome subunit antisecretory factor (AF) abolishes sickness and death in rats subjected to experimental HSV-1 encephalitis (HSE) (Jennische et al 2008)
We found that HSV-1 is able to induce similar complexes of proteasomes and complement factors 3 and 4 (C3 and C4)

Summary

Introduction

Herpes simplex virus type 1 (HSV-1), a usually benign virus that commonly causes recurrent oral lesions, may occasionally induce a necrotizing encephalitis focused on the frontotemporal regions of the brain. The ubiquitin-proteasome pathway degrades defective and foreign proteins and plays an important role in a wide variety of cell functions including antigen processing, transcription regulation, cell cycle regulation, and DNA repair. We have previously shown that a peptide derived from the proteasome subunit antisecretory factor (AF) abolishes sickness and death in rats subjected to experimental HSE (Jennische et al 2008). This counteraction of the lethal encephalitis is most likely accomplished by lowering the. As a general designation of the complex between complement factors and proteasomes, we here introduce the term Bcompleasome^

Materials and methods

Results and discussion

Compliance with ethical standards