Xenotropism: The elusive viral receptor finally uncovered

Almost 30 years ago, virologists working with RNA tumor viruses (now called retroviruses) were faced with the dilemma of determining the nature of the RNA tumor viruses detected by electron microscopy in the tissues of the New Zealand Black (NZB) mouse. This widely studied murine strain, derived in the 1950s by Marianne Bielschowsky (1), develops autoimmune disorders and B cell lymphomas. Because similar RNA tumor viruses [also known as murine leukemia viruses (MLVs)] were associated with leukemias and lymphomas in many animal species, characterizing the NZB virus offered a clue to the potential causative agent for NZB disease. However, all attempts to grow the NZB virus by standard procedures in cultured mouse cells failed; the virus was considered “replication-defective”.

Working with knowledge gained from pioneers in the RNA tumor virus field (2), the biologic activity of this NZB virus ultimately was demonstrated in 1970 by cultivating NZB mouse embryo cells with hamster or rat tumor cells containing a nonreplicating sequence of the murine sarcoma virus (3). This procedure, using conventional MLV, leads to the rescue of the sarcoma virus genome in the envelope coat of the replication-competent MLV (2). The newly formed transforming virus pseudotype now has the host range of the “helper” MLV. Supernatants from the NZB cell coculture demonstrated the presence of a replicating virus that could induce foci of transformation in rat cells but not mouse embryo cells (3). The NZB MLV host range thus seemed limited to rat cells. Subsequent work demonstrated that the helper MLV visualized in the NZB mouse cells was infectious but was not infectious at all for mouse cells (i.e., complete block). It was infectious only for cells from heterologous species, including those of avian origin (Table 1). Similar viruses were subsequently found in all laboratory strains of Mus musculus domesticus as …