Reaction of complement factors and proteasomes in experimental encephalitis

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.