Phenotypic mixing of retroviruses in mitogen-stimulated lymphocytes: analysis of xenotropic and defective endogenous mouse viruses.

In addition to the known induction of xenotropic endogenous virus in B-mitogen-stimulated murine lymphocyte cultures, distinguishable defective viruses were also induced in different mouse strains (NFS/N, 129, BALB/c). AKR cells produced xenotropic virus and also, in contrast to BALB/c, ecotropic virus. The drug bromodeoxyuridine appeared to have differential effects on virus expression, amplifying xenotropic virus induction but inhibiting the spontaneous production of the ecotropic virus in AKR cultures and of the defective virus in NFS/N cells. Infecting stimulated BALB/c or AKR cultures with Friend leukaemia virus resulted in the production of ecotropic-xenotropic pseudotype viruses, indicating that the infecting ecotropic virus replicates in the cells in which xenotropic virus is induced. No pseudotypes or recombinants were observed following infection of spleen cells releasing defective viruses. Friend leukaemia virus and xenotropic virus with an ecotropic envelope replicated equally well in stimulated lymphocytes from the different strains examined. Taken together, these findings indicate that the non-infectious viruses are encoded by defective proviruses, rather than resulting from faulty, host cell-controlled, virus maturation.