Feline calicivirus (FCV) is a virus of the family Caliciviridae that causes disease in cats. It is one of the two important viral causes of respiratory infection in cats, the other being Felid alphaherpesvirus 1. FCV can be isolated from about 50% of cats with upper respiratory infections. Cheetahs are the other species of the family Felidae known to become infected naturally. Viral structure and pathogenesis Different strains of FCV can vary in virulence (the degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host). Being an RNA virus, FCV has a high elasticity of its genome, which makes it more adaptable to environmental pressures. This not only makes the development of vaccines more difficult, but also allows for the development of more virulent strains. In persistently infected cats, the gene for the major structural protein of the viral capsid (the outer protein coat of a mature virus) has been shown to evolve through immune-mediated positive selection, which allows the virus to escape detection by the immune system. A form of FCV has been found to cause a particularly severe systemic disease in cats, similar to rabbit hemorrhagic disease (which is also caused by a calicivirus). This virus has been called virulent systemic feline calicivirus (VS-FCV) or FCV-associated virulent systemic disease (VSD). The disease is caused by direct viral invasion of epithelium and endothelium and secondary host immune response. Strains of VS-FCV have seemingly risen independently of one another since first being described, meaning that not all cases of VS-FCV have spread from a single case. Most of the outbreaks of VS-FCV have been reported in the United States. It was originally described in 1998 in Northern California. The prevalence of FCV varies depending on the environment. In private households, FCV is present in about 10% of cats (either in active or carrier state), while the prevalence in shelters or catteries is 25 to 40%. FCV replicates in the oral and respiratory tissues, and is secreted in saliva, feces, urine, and respiratory secretions. It can be transmitted through the air, orally, and on fomites. Infected cats usually shed the virus for two weeks. Following this period, infected cats never shed the virus again or become latently infected and shed the virus continuously or intermittently. Co-infection with either feline herpesvirus