Animal models for
severe acute respiratory syndrome-
coronavirus infection of humans are needed to elucidate SARS
pathogenesis and develop vaccines and antivirals. Transgenic mice were developed expressing human angiotensin-converting
enzyme 2, a functional
receptor for the
virus, under the regulation of a global
promoter. A transgenic lineage, designated AC70, was among the best characterized against
SARS coronavirus infection, showing
weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of
virus replication. In contrast, infected
transgene-negative mice survived without showing any clinical illness. The severity of the
disease developed in these transgenic mice, AC70 in particular, makes these mouse models valuable not only for evaluating the
efficacy of antivirals and vaccines, but also for studying
SARS coronavirus pathogenesis and infection by other coronaviruses utilizing human ACE2 for
viral entry into cells.