Deer Mice as Immunological Tools for Infectious Disease

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DESCRIPTION (provided by applicant): Hantavirus cardiopulmonary syndrome (HCPS) is an emerging infectious disease characterized by the presence of inflammatory cytokine-producing T cells in the lungs of infected patients. Most cases of HCPS in North America are caused by Sin Nombre virus (SNV), although more than a dozen other hantaviruses are known to cause HCPS in North and South America. Regardless of the viral etiology, virtually no cytopathic effect is observed in infected capillary endothelial cells, indicating that the disease is a cytokine-mediated immunopathology. In contrast, deer mice (Peromyscus maniculatus), the natural host of SNV, exhibit no pathology when infected and remain persistent carriers, perhaps for life. Although their lungs contain replicating virus, no pulmonary inflammation is observed, indicating that the immune system has evolved a nonpathogenic response for containing SNV. It is unknown how deer mice engage SNV. We have initiated a research program to develop molecular and cellular assays to detect immune functions and cytokine responses in deer mice. These techniques will be used to elucidate the mechanisms of persistent infection of Sin Nombre virus (SNV) in deer mice. We have developed the methods for long-term culturing of T cell lines from outbred deer mice and are currently working to establish lines from 19 experimentally-infected deer mice. These lines will be examined for their cytokine profiles by real-time PCR to determining their immunological phenotypes (i.e., Th1, Th2, Treg). We will also examine the T cell responses in wild deer mice naturally-infected with SNV to determine if natural infection parallels that of experimental infection. Identification of the strategies employed by deer mice to contain infection without pathology could provide insight into the clinical management of HCPS.