| Our current understanding of Sin Nombre (SN) virus infection in its natural reservoir, the deer mouse (Peromyscus maniculatus), is not very advanced. This is due, in part, to the absence of an experimental animal infection model for this virus. To date our knowledge of this important infection process has been derived solely from observational field studies. This manuscript describes the establishment of an experimental infection model for SN virus in the deer mouse and the provocative studies carried out using this model to address several aspects of SN virus infection in the its natural reservoir, including virus-induced pathology, viral shedding, and the kinetics of infection.; In order to safely conduct experiments using infected deer mice we constructed a novel outdoor biocontainment facility. The facility enabled us to safely house both wild-caught and laboratory-reared deer mice through all seasons. We quarantined wild-caught deer mice from New Mexico in the outdoor facility to assess their true infection status and used mice that remained seronegative after quarantine to establish a laboratory-breeding colony.; A new strain of SN virus, SN77734, was isolated via intramuscular inoculation of laboratory-reared deer mice with a tissue homogenate prepared from a naturally infected deer mouse. This isolate allowed us to develop a controlled model of infection that we used to define the natural history and kinetics of infection. During acute infection there was widespread dissemination of viral RNA and viral nucleocapsid antigen throughout the host, with heart, lung, and brown fat consistently carrying the highest levels of viral RNA. Viral RNA titers peaked by d 21 in most tissues, then declined coincident with the appearance of high titers of neutralizing antibodies. We found that SN virus developed a chronic infection in the host, with viral distribution limited largely to the heart during the later stages of infection, suggesting that this tissue may be an important site for viral maintenance. In addition, the prominent involvement of the heart, lung, and brown fat during the acute phase of infection suggests that these tissues may be important sites for early virus replication. We noted no consistent histopathological changes associated with the acute phase of infection, even when viral RNA load was high.; To address mechanisms of viral transmission, we examined experimentally infected deer mice for their ability to shed SN virus in urine, feces, and saliva. We found no evidence of infectious virus shed in these secretions and excretions during acute or chronic infection, despite finding significant levels of viral RNA in the salivary gland and kidney during the acute phase of infection. These data indicate that viral shedding is intermittent and/or virus spreading may be regulated by factors that we are unable to replicate in the experimental model. |
