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J. Virol. doi:10.1128/JVI.01967-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Participation of both host and virus factors in induction of severe acute respiratory syndrome in F344 rats infected with SARS coronavirus

Departments of Pathology and Virology I, and Center for Pathogen Genomics National Institute of Infectious Diseases, Tokyo, Japan

^* To whom correspondence should be addressed. Email: nnagata{at}nih.go.jp,

	Abstract

To understand the pathogenesis and develop an animal model of severe acute respiratory syndrome-associated coronavirus (SARS-CoV), the Frankfurt 1 SARS-CoV isolate was passaged serially in young F344 rats. Young rats were susceptible to SARS-CoV, but cleared the virus rapidly within 3 to 5 days of intranasal inoculation. After 10 serial passages, replication and virulence of SARS-CoV were increased in the respiratory tract of young rats without clinical signs. By contrast, adult rats infected with the passaged virus showed respiratory symptoms and severe pathological lesions in the lung. Levels of inflammatory cytokine in sera and lung tissues were significantly higher in adult F344 rats than in young rats. During in vivo passage of SARS-CoV, a single amino acid substitution was introduced within the binding domain of the viral spike protein recognizing angiotensin-converting enzyme 2 (ACE2), known as a SARS-CoV receptor. The rat-passaged virus more efficiently infected CHO cells expressing rat ACE2 compared to the original isolate. These results strongly indicate that host and virus factors such as respective advance age and virus adaptation are critical for development of SARS in rats.

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