Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus Y. Xiao*,†, Q. Meng*,†, X. Yin*, Y. Guan*, Y. Liu*, C. Li*, M. Wang*, G. Liu*,†, T. Tong*,†, L.-F. Wang‡, X. Kong*,† and D. Wu*,† *National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences (CAAS), Harbin 150001, China, †Graduate School of CAAS, Beijing 100081, China and ‡CSIRO Livestock Industries, Australian Animal Health Laboratory, Australian Biosecurity Cooperative Research Centre for Emerging Infectious Diseases, Geelong, Victoria 3220, Australia Summary Masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (SARS-CoV). Infected animals become less aggressive and develop pyrexia, lethargy and diarrhoea. The pres- ent study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with SARS-CoV. In-situ hybridization (ISH) with probes specific for the RNA polymerase gene demonstrated viral RNA in the lung, small intestine and cerebrum only. In-situ labelling was employed in order to demonstrate cellular apoptosis in the cerebrum, but there was no evidence of apoptosis within the myocardium. These results indicate that SARS-CoV causes multi-organ pathology in civets, similar to that observed in human SARS patients. These parallels suggest that civets may be used as an animal model of this infection to gain insight into the pathogenesis of SARS and for evaluation of candidate vaccines and antiviral drugs. � 2008 Elsevier Ltd. All rights reserved. Keywords: apoptosis; civet; in-situ hybridization; SARS coronavirus Introduction Severe acute respiratory syndrome (SARS) first emerged in Guangdong Province in the People’s Republic of China in November 2002. The aetiologi- cal agent of this syndrome was a newly emerged and previously unrecognized coronavirus, now known as SARS coronavirus (SARS-CoV) (Kuiken et al., 2003; Ksiazek et al., 2003). SARS is an acute pulmo- nary syndrome characterized by atypical pneumonia, progressive respiratory failure and death in up to 10% of infected individuals (Poon et al., 2004). Although the SARS epidemic has subsided, many authorities, including the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC), have warned of the possible re- emergence of this highly infectious disease. It is therefore imperative that effective measures to pre- vent and treat the disease are developed and evalu- ated. To achieve this goal, animal models will play an essential role in studying the pathogenesis of SARS-CoV infection and in developing effective vaccines and therapeutics. A wide range of animal species has been confirmed to be susceptible to experimental infection with SARS-CoV, including rodents (mice and hamsters), carnivores (ferrets and cats) and non-human primates (Wang et al., 2006). Adult mice infected with SARS- CoV via the respiratory tract show no clinical signs of disease and only mild respiratory tract inflammation (Subbarao et al., 2004). Aged mice, hamsters and ferrets do show signs of clinical disease such as weight loss and ruffled fur but do not develop lung pathology (Martina et al., 2003; Roberts et al., 2005a,b). Two groups of investigators have studied SARS-CoV Correspondence to: X. Kong (e-mail: