We have discovered the first murine calicivirus, which we have designated Mouse Calicivirus 1 or MCV 1. An important and unique property of MCV 1 is that it infects and causes disease in laboratory mice, thereby presenting the opportunity to study calicivirus pathogenesis and immunity in a well characterized small animal model. Human caliciviruses such as Norwalk virus are major causes of epidemic gastroenteritis in adults, and thereby cause significant morbidity and economic loss. Studies of caliciviruses in cats and pigs have led to important advances in the understanding of calicivirus biology and pathogenesis. However, basic questions regarding virulence determinants, cell tropism, and mechanisms of immunity remain unanswered. Moreover, and important to human health, it is not known whether it is possible to effectively vaccinate against these agents, and mechanisms of vaccination are undefined. Thus, the lack of a small animal model with extensive genetic and immunologic tools for the analysis of pathogenesis and immunity has held back research on these important viruses. The discovery of MCV 1 thereby affords new opportunities for basic research into calicivirus virology and immunology. To date we have sequenced the new virus and found that it is in the Norwalk-like genus of caliciviruses, shown that gradient purified virus induces disease, expressed the capsid protein in baculovirus and shown that it assembles into virus like particles (VLPs), shown that the virus replicates in various tissues and is shed in stools after intranasal, peroral, or intracranial inoculation, and shown that (surprisingly) the virus does not kill T and B cell deficient mice but does kill mice deficient in STAT1 or interferon (IFN) receptors. Based on these results we propose to pursue the following Aims.
Aim 1. Characterize MCVl and develop a reverse genetic system for MCV1.
Aim 2. Determine the role of the innate immune response in control of MCV1 infection.
Aim 3. Determine the role of the adaptive immune response in clearance of, and vaccination against, MCV1 infection. ? ?
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