Lymphocytic choriomeningitis virus (LCMV) infections of Syrian golden hamsters

An acutely lethal LCMV disease model has been established in the Syrian golden hamster (Mesocricetus auratus) in which lethality and disease are dependent upon both the inbred hamster strain and the LCMV strain. Young adult inbred, male and female, hamsters were tested for lethal-disease susceptibility by lymphocytic choriomeningitis virus (LCMV) strains, WE or Armstrong (ARM). With WE inocula, PD4 and MHA inbred hamsters were highly susceptible to a wasting disease. LVG and LHC inbred hamsters were intermediate in susceptibility; some of these animals died of wasting illness, and others exhibited minimal disease and survived. CB and LSH hamsters were highly resistant to any disease by WE. Mean survival times of susceptible hamsters given lethal WE inocula approximated 2.5 weeks and were not dependent on virus dose. By 1.5 weeks after WE inoculation wasting disease signs were notable and consisted of lethargy, progressive body weight loss, and diarrhea. The LCMV strain, ARM, was avirulent for all hamster strains, causing neither death nor disease. Hamsters surviving WE or ARM inoculation appeared healthy, produced LCMV antibody, and acquired resistance to further lethal WE challenge. Despite hamster-lethality differences, WE and ARM appeared comparably immunogenic for all hamster strains, based on host antibody titers. A number of other differences between the LCMV strains were, however, noted which could be relevant to virus virulence and lethality for hamster hosts. These included guinea pig lethality, temperature sensitivity, and plaque morphology. o 1987 Society for Experimental Biology and Medicine. Lymphocytic choriomeningitis virus (LCMV) infections of Syrian golden hamsters (Mesocricetus auratus) have long been recognized (1-23) and a concern in the epidemiology of human-LCMV outbreaks ( 10-22). Yet, previous studies on the mortality and virulence of LCMV for hamsters are not consistent. It is well documented that LCMV-inoculated adult and neonatal hamsters may undergo an inapparent, immunizing infection (1, 2, 5-7, 9-16, 20, 21). However, some reports allude to signs of illness among hamsters with immunizing nonlethal LCMV infections, but give few details ( 5 , 10, 12). In addition to inapparent LCMV infections, virus-inoculated neonates may succumb to an acutely lethal illness ( 5 , 9) or develop chronic vasculitis (9, 24). In LCMV-inoculated adult hamsters acute illness and death have also been observed ' E.V. G. was funded by the Resident Research Associateship program of the National Research Council and is the author to whom correspondence should be addressed: Plum Island Animal Disease Center, USDA-ARS, P.O. Box 848, Greenport, NY 11944. (3,4, 8, 13). But these later studies emphasized the benign nature of infection and the episodes of lethal illness among the LCMV-inoculated hamsters were not considered a consequence of viral etiology (1, 9, 13). Confusion regarding LCMV lethality for hamsters may be due to the variability of virus strains and the genetic background of animals used in those studies. LCMV strains exhibit a marked range of biological and molecular heterogeneity which can affect their virulence potential for the appropriate host (16, 22, 23, 25-31). Furthermore, in this regard, the genetic background of hamster strains has proven to be a factor in the use of these animals as model hosts for studies of resistance and susceptibility to oncologic, microbial, and viral diseases (32-37). Because of such host-virus strain variability, a systematic study into the establishment of a uniformly lethal LCMVdisease model in the hamster was pursued. The susceptibility and resistance of young adult, female and male, inbred hamsters to LCMV mortality following intraperitoneal (ip) inoculation of either the WE strain, a virus highly virulent for rodents, or the Armstrong (ARM)