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Lymphomas and high-level expression of murine leukemia viruses in CFW mice
L Taddesse-Heath1, S K Chattopadhyay, D L Dillehay
1Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0760, USA.
Abstract:
Historically, Swiss Webster mice of the CFW subline, both inbred and random-bred stocks, have been considered to have a low spontaneous occurrence of hematopoietic system tumors, and previous reports of infectious expression of murine leukemia viruses (MuLVs) have been rare and unremarkable. In marked contrast, in the present study of CFW mice from one source observed by two laboratories over a 2-year period, nearly 60% developed tumors, 85% of which were lymphomas, the majority of B-cell origin. All tumors tested expressed ecotropic MuLVs, and most expressed mink cell focus-inducing (MCF) MuLVs. Among normal mice of weanling to advanced age, over one-half were positive for ecotropic virus in tail or lymphoid tissues, and MCF virus was frequently present in lymphoid tissue, less often in tail. Patterns of ecotropic proviral integration indicated that natural infection occurred by both genetic and exogenous routes. Lymphomas were induced in NIH Swiss mice infected as neonates with tissue culture-propagated MuLVs isolated from normal and tumor tissue of CFW mice.
Insights
Swiss Webster mice unexpectedly developed high rates of lymphoma tumors, linked to murine leukemia virus (MuLV) infections. Natural MuLV infection occurred through genetic and external routes, causing lymphomas in susceptible mice.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Swiss Webster mice (CFW subline) historically showed low spontaneous hematopoietic tumors.
- Previous reports of infectious murine leukemia viruses (MuLVs) in this strain were rare.
Purpose of the Study:
- Investigate the high incidence of tumors in CFW mice.
- Characterize the role of MuLVs in tumor development.
- Determine the origin and transmission routes of MuLV infection.
Main Methods:
- Longitudinal observation of CFW mice over 2 years across two laboratories.
- Tumor analysis, including lymphoma characterization (B-cell origin).
- Detection and characterization of ecotropic and mink cell focus-inducing (MCF) MuLVs in tumors and normal tissues.
- Analysis of ecotropic proviral integration patterns.
- Experimental induction of lymphomas in NIH Swiss mice using CFW-derived MuLVs.
Main Results:
- Nearly 60% of CFW mice developed tumors, predominantly lymphomas (85%) of B-cell origin.
- All tested tumors expressed ecotropic MuLVs; most also expressed MCF MuLVs.
- Over 50% of normal mice were positive for ecotropic virus; MCF virus was common in lymphoid tissues.
- Proviral integration patterns suggested both genetic and exogenous MuLV infection routes.
- Infected NIH Swiss mice developed lymphomas.
Conclusions:
- CFW mice from a specific source exhibit a high susceptibility to MuLV-induced lymphomas.
- Natural MuLV infection is prevalent and can occur exogenously or genetically.
- MuLVs, particularly ecotropic and MCF types, play a critical role in lymphoma pathogenesis in this mouse model.