Highly virulent strains of feline calicivirus (FCV) have caused at least six outbreaks of a newly recognized fatal disease in cats. Although these outbreaks have been limited in extent, there is a real risk that these hypervirulent FCV strains will spread to the general cat population. FCV is highly contagious and may persist in the tonsils of infected cats that recover from disease. The goal of our proposed studies is to identify markers by which hypervirulent FCV can be distinguished from the more common, but less virulent FCV strains. Currently, there is no way to distinguish between strains of differing virulence; therefore, the prevalence of hypervirulent FCV in cats cannot be determined and consequently control measures cannot be undertaken to identify and isolate carrier cats. We propose to examine a large panel of FCV strains in the laboratory for differences in selected genetic, physical, and viral growth properties that correlate with their natural virulence for cats. In preliminary studies, we have found that a hypervirulent FCV strain is more stable at room temperature and grows more rapidly in cell culture than less virulent strains. We believe that these differences will be found in other hypervirulent strains. If we are correct, then we will use genetic techniques to identify the specific genome sequence(s) of FCV responsible for hypervirulence with the longer-term goal of developing a simple screening assay to identify hypervirulent strains and determine their prevalence in the general cat population, allowing more effective control programs to be developed.