Severe acute respiratory syndrome (SARS), caused by a new human coronavirus (SARS-CoV), represents the 21st century's first pandemic caused by a previously unknown etiological agent. The 2002-03 SARS epidemic stimulated research on coronaviruses of humans, animals, and birds. SARS had enormous economic impact and demonstrated the pathogenic potential of this large group of RNA viruses. An indirect result of the SARS epidemic was the discovery of two new human coronaviruses, HCoV-NL63, isolated in 2004, and HCoV-HKU1, discovered in 2005, and the discovery of novel bat coronaviruses in Asia. Interestingly, preliminary phylogenetic analysis suggests that all animal and human coronaviruses may have evolved from progenitor coronaviruses in bats. Studies on the epidemiology and pathogenesis of NL63, HKU1, and bat coronaviruses are still in their infancy. My mentor's laboratory has extensive experience in studying human and animal coronaviruses. Because I am a pediatric infectious disease specialist with a collaboration already established with The Children's Hospital Clinical Virology Laboratory, an outstanding collection of pediatric respiratory and stool specimens is available to me. Additionally, my mentor and I have joined the recently formed Rocky Mountain Bat Research Consortium. These combined advantages provide me with the needed resources and training for this proposed research. In this revised K08 application, I propose epidemiological, functional and molecular characterization studies on NL63, HKU1, and novel Rocky Mountain bat coronaviruses (RM-BtCoV), which I recently discovered. My goals are to develop sensitive and specific new tools for the rapid diagnosis of these viruses; characterize their prevalence, diversity and clinical spectra; and identify candidate receptor(s) for RM-BtCoVs. These studies will generate needed and valuable reagents for further studies on these viruses, provide information regarding the roles of NL63 and HKU1 in pediatric diseases, and provide further insights into the evolutionary relationships of coronaviruses and mechanisms of emergence of zoonotic diseases. The training and research on emerging coronaviruses that I propose here will enable me to study the essential components of emerging infectious diseases caused by other viruses, including their epidemiology, ecology, diagnostics, disease associations, and zoonotic emergence. ? ? ?
