Differential chemokine induction by the mouse adenovirus type-1 in the central nervous system of susceptible and resistant strains of mice.
Mouse adenovirus-type 1 (MAV-1) has recently been shown to cause a fatal hemorrhagic encephalopathy in certain strains of mice whereas other strains are resistant. Morbidity is associated with a productive infection of cerebrovascular endothelial cells, resulting in necrosis of the vasculature, infarction, hemorrhage and death within 4 - 6 days. Previous studies were not able to define a role for the innate or acquired immune response. In the current study we have addressed the effect of MAV-1 on chemokine and chemokine receptor expression in the central nervous system (CNS) and spleen of susceptible (C57BL/6) and resistant (BALB/c) strains of mice. Intra-peritoneal infection with MAV-1 in C57BL/6 animals resulted in early and prominent induction of IP-10/crg-2 in the spleen and CNS. Increased expression of MCP-1, MIP-1alpha, MIP-1beta and RANTES was also noted in the CNS of MAV-1-infected C57BL/6 animals commencing around 72 h post-infection. In contrast, chemokine expression in BALB/c animals was more restricted with prominent upregulation only of MIP-2 in the CNS. In situ hybridization identified the vascular endothelium and CNS glia as the principal site of IP-10/crg-2 production in the C57BL/6 animals. The chemokine receptors CCR1-5 were upregulated in the CNS of both strains of mice. These data show that productive infection of the CNS with MAV-1 leads to the upregulation of a characteristic pattern of chemokines and their receptors, which may point to a role for these factors in disease pathogenesis.
Charles
P C
PC
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Chen
X
X
Horwitz
M S
MS
Brosnan
C F
CF
D000257:Adenoviridae Infections / Q000378:metabolism*; D000818:Animals; D001927:Brain Diseases / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D007739:L Cells; D017921:Mastadenovirus; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013997:Time Factors
D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019707:Receptors, Chemokine