Natural history of M-MSV tumors in mice carrying endogenized Moloney leukemia virus.

Abstract

The conservation of endogenous type CDNA provirus sequences throughout evolution has raised the question of whether or not they exert normal physiological functions. Among the different hypotheses advanced has been suggested that a genetically transmitted virus could serve to protect the host, possibly via immune reactions, against related, more virulent viruses that may be acquired from the outside [14]. No substantial evidence for this hypothesis has been provided, however. Years ago during studies aimed at investigating in vivo interaction between endogenous and exogenous type C murine retroviruses, we noticed that AKR mice which had been injected with Moloney murine sarcoma virus (M-MSV) developed tumors with a longer latent period than that observed in mice of conventional strains. Furthermore, these late appearing tumors showed an unusual growth pattern, which was characterized by a slow but continuous progression until the host’s death [2]. Subsequently, these findings were confirmed in larger studies using different mouse strains [4, 7, 8]. Figure 1 depicts the general pattern of tumor behavior that has emerged; mice characterized by early endogenous ecotropic virus activation are resistant to early M-MSV oncogenesis, but late appearing progressive tumors are observed in the majority of strains. While late tumor progression is probably due to immunological tolerance of cytotoxic T-lymphocytes (CTL) toward virus-coded antigens [6], the mechanism underlying resistance to early tumor induction is still poorly understood. BALB/Mo mice, which carry the exogenous Moloney leukemia virus (M-MuLV) as an endogenous virus integrated at a single locus (Mov-1) on chromosome 6 [1, 11], offer the unique opportunity of studying whether the full expression of genetically transmitted M-MuLV confers resistance against the antigenically related (M-MuLV) M-MSV complex. Indeed, in a first series of experiments [9], it was found that the natural history of induced tumors in these mice is quite similar to that observed in AKR type mice. In addition, resistance to early tumors appears related to the time course of M-MuLV activation as well as to the presence in the serum of normal mice of antibodies possessing specific binding capacity to M-MuLV surface determinants. The possibility that this particular tumor pattern might be influenced by these antibodies, or by virus-specific CTL activity, is discussed in this study.KeywordsVirus NeutralizationNatural AntibodyProvirus SequenceLonge Latent PeriodEndogenous TypeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.