A low-molecular-weight substance found naturally in mouse serum neutralizes mouse xenotropic Ctype virus. It has no effect on endogenous ecotropic viruses. This neutralizing factor does not belong to the known immunoglobulin classes, and its activity is not associated with the antivirus immunoglobulins that can be detected by radioimmunoprecipitation. Preparations of xenotropic virus absorb out this neutralizing activity in mouse sera. The specificity of this factor for X-tropic virus suggests that it represents a newly recognized type of response of the host to an endogenous virus. Its possible role in the regulation of endogenous C-type viruses is considered.The genomes of murine C-type RNA viruses (MuLV) are integrated as DNA copies in the chromosome of the mouse and can be passed by the germ cell to successive generations (i.e., endogenous virus) (1-4). Production of these endogenous viruses by mouse cells may occur spontaneously or after activation by a variety of experimental means (5-8). Two classes of MuLV that are based on host range have been described in laboratory and certain wild strains of house mice: ecotropic and xenotropic (9-11). The ecotropic viruses, exemplified by the AKR isolates (12), have been recovered from many, but not all, strains of mice; they productively infect mouse cells and can give rise to malignancy in the mouse (2, 10-12). The xenotropic viruses (X-tropic), originally described in New Zealand Black (NZB) mice (13), are probably present in all strains of the Mus musculus species (8-11, 13-15); they have an envelope coat antigen distinct from ecotropic viruses (9-11). Although produced endogenously by mouse cells, these X-tropic viruses cannot productively infect mouse cells, but are infectious for a wide variety of heterologous mammalian and avian cells (16). The role of X-tropic viruses in any pathologic process in the mouse is unknown.
Radioimmunoprecipitation (RIP) techniques have indi-cated the natural occurrence of immunoglobulins of the IgM and IgG classes in most mouse sera; these immunoglobulins will bind to both ecotropic and xenotropic viruses (17, 18). However, these same mouse sera neutralize only xenotropic viruses, not ecotropic viruses (10,11,(19)(20). In general, the titer of neutralizing activity against X-tropic viruses varies between 1:100 and 1:400, but titers may reach levels as high as 1:10,000 (11, 21). Titers of antiviral immunoglobulins, as determined by RIP, range between 10 and 5000, depending on the mouse strain (22). It was assumed that the mouse immunoglobulins (Ig) whose binding to virus could be detected by RIP were responsible for the neutralization of X-tropic virus. The specificity of neutralization, however, could not be explained, inasmuch as these mouse Ig bind equally to both classes of MuLV
