Following intranasal administration, the serious acute respiratory symptoms (SARS) coronavirus replicated

Following intranasal administration, the serious acute respiratory symptoms (SARS) coronavirus replicated to high titers in the respiratory tracts of BALB/c mice. of vaccines, immunotherapy, and immunoprophylaxis regimens. Serious acute respiratory symptoms (SARS) is certainly a serious respiratory illness the effect of a recently determined pathogen, the SARS coronavirus (SARS-CoV) (2, 6, 8, 13). The disease emerged in southern China in late 2002 and spread to several countries within Asia and to Europe and North America in early 2003. The syndrome is characterized by fever, chills or rigors, headache, and nonspecific symptoms such as malaise and myalgias, followed by cough and dyspnea (2, 5, 15). According to the World Health Business, 8,437 cases of SARS had been identified worldwide as of 11 July 2003 and 813 patients had died, resulting NSC-207895 in an overall mortality rate of 9.6% (World Health Organization, Respiratory tract disease progresses to acute respiratory distress syndrome, requiring intensive care and mechanical ventilation for more than 20% of patients (9, 15, 16). Prolonged hospitalizations associated with complications have been reported (9, 15). Public health steps, including early admission, contact tracing, quarantine, and travel restrictions, were instituted to control the spread of the disease (5), and the World Health Business declared that this outbreak was over in July 2003. The severe morbidity and mortality associated with SARS make it imperative that effective means to prevent and treat the disease be developed and evaluated, especially since it is not known whether the computer virus will reappear and display a seasonal NSC-207895 design of flow like various other respiratory pathogen pathogens or whether it’ll be separately reintroduced in to the individual population. Avoidance and treatment strategies could be created predicated on concepts that connect with various other pathogens, but evaluation of NSC-207895 the efficacy of these strategies requires animal models. Coronaviruses are generally restricted in their host range, and viruses associated with disease in SPTBN1 one species can be limited in their ability to replicate in other species (examined in reference 12). NSC-207895 SARS-CoV differs from this general pattern because it is likely an animal computer virus that infects humans. Although closely related viruses have been isolated from animal species in southern China, it is not clear which animal species represents the reservoir from which the computer virus entered the human population (11). Cynomolgus macaques have been reported to develop pathological findings of pneumonia and have been proposed as an animal model for SARS (14). However, small-animal models, such as rodents, would be very useful for evaluating vaccines, immunotherapies, and antiviral drugs, and we have recognized the mouse as a useful animal model for this purpose. MATERIALS AND METHODS Computer virus and cells. L. J. Anderson and T. G. Ksiazek from your Centers for Disease Control and Prevention (CDC), Atlanta, Ga., kindly provided the SARS-CoV (Urbani strain) used in this study (13). The computer virus was isolated and passaged twice in Vero E6 cells at the CDC and was passaged in Vero cells for two additional passages in our laboratory to generate a computer virus stock with a titer of 106.5 50% tissue culture infective doses (TCID50)/ml. The Vero cells were managed in OptiPro SFM (Invitrogen, Carlsbad, Calif.). All work with infectious computer virus was performed inside a biosafety cabinet, in a biosafety containment level 3 facility, and personnel wore powered air-purifying respirators (HEPA AirMate; 3M, Saint Paul, Minn.). Animal studies. The mouse studies were approved by the National Institutes of Health Animal Care and Use Committee and were carried out in an approved animal biosafety level 3 facility. All personnel entering the facility wore powered air flow purifying respirators (HEPA AirMate). Female BALB/c mice 4 to 6 6 weeks NSC-207895 aged purchased from Taconic (Germantown, N.Y.) were housed four per cage. Mice that were lightly anesthetized with isoflurane were inoculated with 50 l of diluted computer virus intranasally. On days 1, 2, 3, 5,.