Differential behavior of the Mo + PyF101 enhancer variant of Moloney murine leukemia virus in rats and mice.
The Mo + PyF101 enhancer variant of Moloney murine leukemia virus (M-MuLV) has been very useful in investigating M-MuLV leukemogenesis. When inoculated subcutaneously (s.c.) into neonatal mice, Mo + PyF101 M-MuLV is attenuated for development of disease. Previous studies in mice infected with wild-type M-MuLV have revealed several important preleukemic events, including development of splenic hyperplasia, defects in bone marrow hematopoiesis, and in vivo generation of MCF viruses that arise by recombination in the uninfected mouse. Mo + PyF101 M-MuLV is defective in inducing these effects after s.c. inoculation. In the experiments reported here, a study of Mo + PyF101 M-MuLV infection in rats was carried out. Wild-type M-MuLV is leukemogenic in rats, but infected rats do not form MCF recombinants since they lack the necessary endogenous polytropic envelope sequences. Since Mo + PyF101 M-MuLV's leukemogenic defect is correlated with a failure to generate MCF recombinants, it seemed possible that wild-type M-MuLV might not have a leukemogenic advantage over Mo + PyF101 M-MuLV in rats, where MCF recombinants cannot form. Neonatal Fisher F344 rats were inoculated s.c. or intraperitoneally by wild-type and Mo + PyF101 M-MuLVs. Surprisingly, Mo + PyF101 M-MuLV was completely deficient in leukemogenesis in rats when inoculated by either route while wild-type M-MuLV induced lymphoma with the predicted time course. The leukemogenic defect for Mo + PyF101 M-MuLV resulted from a pronounced defect for establishing infection in rats. Further studies of wild-type M-MuLV in rats indicated that infection was confined almost exclusively to the thymus at early times. In mice wild-type M-MuLV establishes substantial infection in other hematopoietic organs such as spleen and bone marrow as well. Thymic infection was also correlated with a decrease in thymic cellularity at early times.
Brightman
B K
BK
Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.
Okimoto
M
M
Kulkarni
V
V
Lander
J K
JK
Fan
H
H
D000818:Animals; D000831:Animals, Newborn; D004742:Enhancer Elements, Genetic; D014644:Genetic Variation; D007942:Leukemia, Experimental / Q000503:physiopathology / Q000821:virology*; D051379:Mice; D008815:Mice, Inbred Strains; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012192:Retroviridae Infections / Q000503:physiopathology / Q000821:virology; D013045:Species Specificity; D013997:Time Factors; D014412:Tumor Virus Infections / Q000503:physiopathology / Q000821:virology