An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo.

Abstract

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+PyF101Mo-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.

Lymphomas and High-Level Expression of Murine Leukemia Viruses in CFW Mice

“…In a separate study (data not shown), at 6 weeks postinfection as neonates with the biologically cloned ecotropic virus, three mice displayed high-level ecotropic MuLV expression in spleen and thymus, and one thymus specimen was positive for MCF MuLV. Thus, as predicted from other studies of exogenous infections (2,13,28), MCF MuLV can be generated in vivo shortly after exogenous infection with CFW ecotropic virus. Induction attempts with cloned ecotropic and MCF viruses will be required to clarify whether both classes, singly or in concert, are lymphomagenic.…”

Enhanced replication and pathogenesis of Moloney murine leukemia virus in mice defective in the murine APOBEC3 gene

“…The gross pathology of the sacrificed animals indicated enlarged thymus, spleen or lymph nodes for animals of all genotypes, characteristic of the lymphoblastic lymphoma induced by M-MuLV in B6 and other mouse strains (Brightman et al, 1991). Molecular diagnosis of the tumors was performed by testing tumor DNAs for rearrangements of T-cell receptor beta (TCRβ), immunoglobulin Mu heavy chain (IgH) and immunoglobulin kappa light chain (IgK) genes.…”

Characterization of a Novel Murine Retrovirus Mixture That Facilitates Hematopoiesis

“…The origins of the disease-inducing defective component of MAIDS virus as well as MCF virus genomes from endogenous viruses have been well documented (5,7,8,20,29,47). What is the possible origin of the RLMuLV mixture?…”