Pathology of Guinea Pigs Experimentally Infected with a Novel Reovirus and Coronavirus Isolated from SARS Patients

Abstract

Guinea pigs were inoculated with a reovirus (ReoV) and coronavirus (SARS-CoV) isolated from SARS patients to determine their potential role in the etiology of SARS. Animals infected with ReoV died between day 22 and day 30 postinoculation (PI) while 70% of the animals inoculated with ReoV and SARS-CoV died between day 4 to day 7 PI. The titer of neutralizing antibodies against ReoV and SARS-CoV ranged from 80 to 160 when the animals were inoculated with the two viruses, respectively, while the titer of the antibodies was just below 10 in coinfections. The animal inoculated with ReoV developed diffuse alveolar damage similar to the exudative and leakage inflammation found in SARS patients, and was characterized by diffuse hemorrhage, fibroid exudation, hyaline membrane formation, and type II pneumocytes hyperplasia in alveolar interstitia. The pulmonary epithelial necrosis, excoriation, and early fibrosis of pulmonary tissue were only observed in ReoV-SARS-CoV groups and in SARS-CoV/ReoV groups. Other typical pathological changes included hemorrhagic necrosis in lymph nodes and spleen and hydropic degeneration in the liver. On the contrary, guinea pigs infected with SARS-CoV only developed interstitial pneumonitis. Our experiment demonstrate that ReoV might be one of the primary causes of SARS, since simultaneous coinfection can duplicate the typical pathological changes similar to that of SARS patients. This guinea pig model may provide a useful animal model for SARS.

T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-γ responses

“…Intriguingly, reovirus T1/L has been found to evoke acute respiratory distress in young mice (Majeski et al, 2003a(Majeski et al, , 2003bLondon et al, 2002). A human reovirus isolated from a severe acute respiratory syndrome (SARS) patient has been recently demonstrated to cause SARS-like symptoms in macaques and guinea pigs Liang et al, 2005). Further insight is needed in reovirus and other viral models on the specific mechanisms by which T-2 and other trichothecenes interfere with cytokine-and Ig-regulated viral clearance and how these are impacted by dose, administration route, and duration of toxin exposure.…”

Studies of Severe Acute Respiratory Syndrome Coronavirus Pathology in Human Cases and Animal Models

“…33,34,37,56,66,67 Although these infected animals lacked severe acute pulmonary illness (in contrast to what is typical of SARS), they showed virologic and serologic evidence of SARS-CoV infection, yet some had mild symptoms and showed evidence of virus shedding. Note, however, that the research groups used different viral isolates to infect these animals (as in the monkey experiments described in the following sections); therefore, it is not clear whether one animal model is better than another for SARS-CoV infection.…”

Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice

“…[17][18][19][20] To understand the pathogenesis of SARS-CoV, the SARS-CoV susceptibility of experimental animals such as monkeys, cats, ferrets, mice, pigs, guinea pigs, ham-sters, chickens, and rats has been investigated. 2,4,[21][22][23][24][25][26][27][28] All of these animals are susceptible to SARS-CoV after intrarespiratory inoculation and exhibit virus excretion in pharyngeal or nasal swabs, histopathological pulmonary lesions, and seroconversion. However, the course of infection in these animals is shorter than that in humans.…”