Neuropathology in Neonatal Mice After Experimental Coxsackievirus B2 Infection Using a Prototype Strain, Ohio-1

• Published in: Journal of neuropathology and experimental neurology Vol. 79; no. 2; pp. 209 - 225
• Main Authors: Ushioda, Waka, Kotani, Osamu, Kawachi, Kengo, Iwata-Yoshikawa, Naoko, Suzuki, Tadaki, Hasegawa, Hideki, Shimizu, Hiroyuki, Takahashi, Kimimasa, Nagata, Noriyo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2020; by American Association of Neuropathologists, Inc
• Subjects: Apoptosis; Infections; Neuropathology; Ohio; Glial pathology; Infection; Animal model; Virus receptor; Neuropathology; Coxsackievirus B; Neonatal infection
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1093/jnen/nlz124

Abstract Coxsackievirus B (CVB) causes severe morbidity and mortality in neonates and is sometimes associated with severe brain damage resulting from acute severe viral encephalomyelitis. However, the neuropathology of CVB infection remains unclear. A prototype strain of coxsackievirus B2 (Ohio-1) induces brain lesions in neonatal mice, resulting in dome-shaped heads, ventriculomegaly, and loss of the cerebral cortex. Here, we characterized the glial pathology in this mouse model. Magnetic resonance imaging revealed an absence of the cerebral cortex within 2 weeks after inoculation. Histopathology showed that virus replication triggered activation of microglia and astrocytes, and induced apoptosis in the cortex, with severe necrosis and lateral ventricular dilation. In contrast, the brainstem and cerebellum remained morphologically intact. Immunohistochemistry revealed high expression of the coxsackievirus and adenovirus receptor (a primary receptor for CVB) in mature neurons of the cortex, hippocampus, thalamus, and midbrain, demonstrating CVB2 infection of mature neurons in these areas. However, apoptosis and neuroinflammation from activated microglia and astrocytes differed in thalamic and cortical areas. Viral antigens were retained in the brains of animals in the convalescence phase with seroconversion. This animal model will contribute to a better understanding of the neuropathology of CVB infection.