An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo.
Moloney murine leukemia virus (Mo-MuLV) induces T-cell lymphoma when inoculated into neonatal mice. This is a multistep process. Early events observed in infected mice include generalized hematopoietic hyperplasia in the spleen and appearance of mink cell focus-inducing (MCF) recombinants; end-stage tumors are characterized by insertional proviral activation of protooncogenes. We previously showed that an Mo-MuLV enhancer variant, Mo+PyF101 Mo-MuLV, has greatly reduced leukemogenicity and is deficient in induction of preleukemic hyperplasia. In this report, we have examined Mo+PyF101 Mo-MuLV-inoculated mice for the presence of MCF recombinants. In contrast to wild-type Mo-MuLV-inoculated mice, Mo+PyF101 Mo-MuLV-inoculated mice did not generate detectable MCF recombinants. This failure was at least partly due to an inability of the MCF virus to propagate in vivo, since a molecularly cloned infectious Mo+PyF101 MCF virus did not replicate, even when inoculated as a Mo+PyF101 Mo-MuLV pseudotype. These results show that the leukemogenic defect of Mo+PyF101 Mo-MuLV is associated with its inability to generate MCF recombinants capable of replication in vivo. This, in turn, is consistent with the view that MCF recombinants play a significant role in Mo-MuLV-induced disease and, in particular, may play a role early in the disease process.
Brightman
B K
BK
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Rein
A
A
Trepp
D J
DJ
Fan
H
H
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003673:Defective Viruses / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D014644:Genetic Variation; D007739:L Cells; D007942:Leukemia, Experimental / Q000382:microbiology*; D051379:Mice; D008908:Mink Cell Focus-Inducing Viruses / Q000235:genetics*; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D011289:Preleukemia / Q000382:microbiology*; D011533:Proviruses / Q000235:genetics