Experimental Infection of Macaques with the Human Reovirus BYD1 Strain: An Animal Model for the Study of the Severe Acute Respiratory Syndrome

Abstract

Experimental studies were performed to determine the role of a newly isolated reovirus (ReoV) from a severe acute respiratory syndrome (SARS) patient in the etiology of this newly described serious respiratory syndrome. Four cynomologus macaques were inoculated with this reovirus (BYD1) in an attempt to replicate the infection and pathology observed in SARS. The body temperature of the infected monkeys was monitored three times a day, and blood and fecal samples were periodically collected for specific immunology determinations. On days 7 and 33 after inoculation, necropsies for pathological accessment and pathogen isolation were performed. The four infected macaques developed a fever on days 3 and 4 after inoculation, and maintainted a febrile state for 4–6 days. The highest temperature in the animals recorded was 40.4°C. After a recovery phase, the macaques developed a second febrile condition. Antibody titers against the reovirus injected by the intravenous route occurred in higher number than those in the nasal cavity. Four macaque monkeys demonstrated diffuse alveolar damage, characterized by hemorrhagic pneumonia, serosanguineous exudates, formation of hyaline membranes, and type II pneumocyte hyperplasia, which were similar to those that have been noted in SARS patients. Lymphocytes decreased in the cortex of the lymph node and in the white pulp of the spleen. ReoV was detected in pneumonic tissue by virus isolation and RT-PCR. The macaques infected with the newly isolated reovirus developed a fever, diffuse alveolar damage and pulmonary interstitial inflammation similar to that noted in SARS patients. This evidence demonstrates that ReoV might have a primary role in the etiology of SARS.