mouse, Apodemus agrarius. Subsequent studies have identified antigenically related viruses that are also capable of causing acute, life-threatening human disease. These include Seoul virus, maintained in the domestic rat, Rattus norvegicus (Lee et al., 1982), and Puumala virus, maintained by the bank vole, Clethrionomys glareolus (Brummer-Korvenkontio et al., 1980).
Seoul virus causes a less severe form of HFRS, while Puumala virus is the cause of nephropathia epidemica, a disease commonly seen in Scandinavia, in the western portion of Russia, and, with increasing frequency, in Western Europe. Seoul virus is distributed virtually anywhere in the world where there are large, uncontrolled populations of R. norvegicus (LeDuc et al., 1986). This virus has been isolated and human infections documented in both North and South America (LeDuc et al., 1984, 1985; Childs et al., 1987; Glass et al., 1990). Undoubtedly, the present-day distribution of Seoul virus had its origin in international commerce and its unwanted rodent passenger, R. norvegicus.
The hantaviruses have also found their way into laboratory rodent colonies, in which they cause chronic, asymptomatic infections (LeDuc, 1987). Serious human disease and death have been documented in animal handlers, scientists, and others who unknowingly have been exposed to hantavirus-contaminated rat colonies. These problems continue to exist today, especially in Asia, where quality control of rodent breeding facilities is not as rigorously monitored as in the United States (Umenai et al., 1979; Desmyter et al., 1983; Lloyd et al., 1984).
The viruses have been spread in laboratory animals in several ways. Inbred strains of infected rats have been distributed to investigators around the world. Transplantable tumors, traditionally maintained in laboratory rats, have been the source of additional rodent and some human infections (Yamanishi et al., 1983). Continuous cell lines may also harbor the viruses, although examination of all rat-origin cell lines held by the American Type Culture Collection failed to identify any hantavirus contamination (LeDuc et al., 1985). The risk of contamination to reagents, such as monoclonal antibodies produced in infected rodent hosts, is currently unknown but clearly plausible. Recent studies have demonstrated that the common house mouse, Mus musculus, may harbor hantaviruses. Hantaviruses have been isolated from domestic mice in Texas (Baek et al., 1988) and in Yugoslavia (Diglisic et al., 1991; T. Avsic-Zupanc, Microbiologist, Institute of Microbiology, Medical Faculty of Ljubljana, Slovenia, personal communication, 1991).
Stopping the distribution of hantavirus-contaminated laboratory animals, cell cultures, or reagents is difficult, since there is no readily available commercial test for screening animals for infection. This issue is discussed more fully below.