Susceptibility of nude mice carrying the Fv-4 gene to friend murine leukemia virus infection

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4(-/-) nude(nu/nu)) by mating them with Fv-4 congenic BALB/c mice (Fv-4(r/r) nude(+/+)) and examined the susceptibility of the F₂ progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4(-/-) nude(nu/nu)) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv- 4(r/r) nude(nu/nu)) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F- MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F₁ mice with the Fv-4(r/-) nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F₁ mice with the Fv-4(r/-) nude(+/+) genotype. However, almost all BALB/c nude mice with the Fv-4(r/-) nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.