In 1993 a virus belonging to the hantavirus genus was identified as the cause of an acute pulmonary syndrome designated as hantavirus pulmonary syndrome. Despite a relatively high incidence of infection with the virus, designated Sin Nombre virus (SNV), in P. maniculatus, the incidence of antibody positivity in humans with occupational exposure is low <1%. This is in contrast to Puumala virus where the incidence of antibody in individuals with the same risk factors is high >20% (r). When infected animals were inadvertently caged with uninfected cage mates they failed to transmit virus. The overall hypothesis that this proposal is addressing is that some unknown factor(s) must be limiting the spread of Sin Nombre virus from P. maniculatus to humans. This may be caused by several factors including: 1) Virus strain variation, 2) Age or physiologic state of the host. 3) Genetic susceptibility of P. maniculatus. 4) State of the virus in infected animals. 5) Route of exposure of deer mice to Sin Nombre virus (ie. horizontal vs vertical transmission). This hypothesis will be pursued by the following specific aims: 1. Field Studies: Field studies will be conducted to identify ecological factors important in the maintenance and distribution of hantaviruses in rodents. This work will be done in collaboration with the Desert Research Institute, and the Biology Department at the University of Nevada and will involve both remote sensing and geographic information systems. 2) Biological characteristics of genetic variants of hantaviruses. Variants will be characterized by a number of criteria including biological properties and serological properties. 3) Genetic variation within P. maniculatus: Preliminary studies indicate that members of the genus Peromyscus can be grouped based on the D loop region of their mitochondrial DNA. This initial studies will be expanded to determine if Peromyscus can be sub-grouped based on their DNA profile (including the use of multilocus probes) and if these subgroups groups relate to the hantaviruses genotypes infecting these animals. 4. Pathogenesis of hantaviruses. The distribution of the virus in various organs and cells will be conducted using in situ hybridization to detect virus RNA, in situ antibody staining for the detection of virus antigens and cocultivation to detect infectious virus. This information will provide important information concerning how virus is transmitted within rodent communities and from humans to rodents.