Pathological changes in masked palm civets experimentally infected by severe acute respiratory syndrome (SARS) coronavirus

Abstract

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 present 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.

Fig. 1

Histopathological changes in infected civets. (a) Interstitial pneumonia at 3 dpi showing protein-rich oedema fluid in the lumina of bronchioles and alveoli. HE, ×200. (b) Interstitial pneumonia at 13 dpi. HE, ×400. (c) Atrophy of splenic lymphoid tissue (arrowed) at 3 dpi. HE, ×200. (d) Depletion of lymphoid follicles in lymph node (arrowed) at 13 dpi. HE, ×200. (e) Congestion and vacuolar degeneration of hepatocytes at 3 dpi. HE, ×100. (f) Neuronal degeneration and neuronophagia (arrowed) in cerebrum at 3 dpi. HE, ×400.

Fig. 2

Detection of SARS-CoV RNA by ISH. For each tissue tested, the left panel shows the result for infected civets whereas the right panel shows the non-infected control. (a) Lung showing labelling of macrophages (arrowed). (b) Small intestine showing labelling of macrophages (arrowed). (c) Glial cells of cerebrum (arrowed). (d) Neuron within the cerebrum (arrowed). (a)–(c), ×1000; (d), ×400.

Fig. 3

Detection of apoptosis in cerebrum. The left panel shows the result for infected civets, whereas the right panel shows the non-infected control. (a) Neuron and (b) glial cells. Arrows indicate cells undergoing apoptosis, ×1000.