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Of mice, cats and baboons ... xmrv related?

Discussion in 'XMRV Research and Replication Studies' started by natasa778, May 21, 2010.

  1. natasa778

    natasa778 Senior Member


    Murine leukemia virus (MLV) and mammalian gamma-retroviruses

    Thymic lymphomagenesis in mice follows activation of endogenous MLV but this was not appreciated until 1970 [50]. In 1933 Jacob Furth bred the AKR mouse strain that has a high probability of developing lymphoma, but MLV was not discovered as a virus until 1951, by Ludwig Gross [7]. AKR mice, carrying two endogenous genomes of N-tropic MLV, can replicate activated virus as they carry a permissive allele of the Fv-1 cellular restriction gene [51]. They begin to release virus spontaneously as late embryos [50].

    Spontaneous release of MLV from uninfected murine cell cultures was observed by Aaronson et al [52]. At the same time as we found we could induce ERV production in chick embryo cells [29] similar experiments were reported for MLV activation by halogenated pyrimidines [53,54]. In fact, radiation-induced lymphomagenesis with virus activation had been reported in mice earlier [55,56]. At that time, however, in vivo activation of a latent exogenous virus could not be distinguished from an endogenous genome in the germ-line. The genetic mapping and analysis of viral gene expression of endogenous MLV was studied in great detail in the 1970s and 1980s [37]. As with endogenous ALV many of the genomes are defective, while others maintain open reading frames or complete, potentially infectious genomes.

    The induction of thymic lymphomas in AKR and other susceptible mice involves more than activation of MLV. The AK virus in viremic mice recombines with other endogenous env genes, and it is these recombinant retroviruses with expanded tropism that elicit malignancy following integration adjacent to proto-oncogenes [57]. There is an analogous situation in cats except that the initiating feline leukemia virus subtype A is an exogenous infection which then forms lymphomagenic recombinants with endogenous env, giving rise to FeLV-B [57].

    With the discovery of endogenous MLV, many investigators in the early 1970s began to examine cells from other species for similar viruses. Reverse transcriptase assays, electron microscopy and nucleic acid hybridization provided useful methods of detection. Many mammalian species were found to harbor gamma-retroviruses related to MLV, including non-human primates. For instance gamma-retrovirus was isolated from trophoblastic cells of the baboon placenta [58]. This virus was found to be very closely related antigenically and by sequence homology to the endogenous RD114 virus in cats (which is itself unrelated to endogenous FeLV). Benveniste and Todaro [59] observed, like we did for jungle fowl, that only certain species of the cat genus, Felis, possessed this endogenous genome related to the baboon ERV. In contrast, all species of baboons [60] carry this virus so it would appear to have been present in the germ line of primates much longer than in cats. Thus it seems evident that a horizontal, infectious event occurred to transfer the virus from baboons to cats, whereupon it became endogenous in the new species (Figure 3).

    thumbnailFigure 3. Exit from and entry into host genomes: transmission of the baboon ERV, BaEV to become the feline ERV, RD114.

    Since cats would be quite likely to scavenge and feed on baboon placentae, a possible exposure to the virus can be envisioned. The human placenta is also permissive to the expression of multiple families of human endogenous retrovirus (HERV) genomes. Indeed, it appears that the retroviral envelope glycoproteins of at least one of them (HERV-W and possibly ERV-3) may be involved in natural syncytium induction to form the syncytiotrophoblast [61-63].
  2. bel canto

    bel canto Senior Member

    Natasa, you are amazing!! What an interesting study. Could this mean that we have the potential to be "trading" these retrovirus between many species? That's a scary thought.

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