Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters

Abstract

Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.

Diffuse Alveolar Lesion in BALB/c Mice Induced with Human Reovirus BYD1 Strain and its Potential Relation with SARS

“…In contrast to the lung lesions observed after inoculation with SARS-CoV alone, there was mild lesion in both the alveolar septa and in the immune system in group 5 mice, a results which agrees with previous reports on KM sucking mice, BALB/c mice, golden Syrian hamsters, cats, ferrets and cynomologus macaques [2,8,12,13,16,18]. These infected animals displayed the atypical pathology of the second and third phases of human SARS patients [2,8,12,13]. SARS-CoV infection suppresses immunity and may predispose infected hosts to secondary infections, such as measles virus infection [8].…”

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.…”

“…54 Syrian golden hamsters developed acute interstitial pneumonia and consolidation after intranasal administration of 10 3 TCID 50 of SARS-CoV. 56 This consolidation, in association with virus replication, was most extensive on day 7 postinfection. Following low-titer SARS-CoV infection, hamsters showed pulmonary lesions, such as inflammatory infiltration with mononuclear cells in the alveolar septa and peribronchial pneumonic consolidations, along with consistently high levels of viral replication.…”

Prior Immunization with Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus (SARS-CoV) Nucleocapsid Protein Causes Severe Pneumonia in Mice Infected with SARS-CoV

“…E, Equal amounts of the gradient fractions (nos. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] were examined by Western blot analyses. m8, m8-infected RK13 cell lysate; ppt, m8rVV-NMES-infected RK13cell lysate; PC, RK13 cell lysates infected with mOrVV-NHis, mOrVV-MHis, mOrVV-EHis, or mOrVV-SHis.…”