Fm. Zhang et al., Resistance to Friend murine leukemia virus infection conferred by the Fv-4gene is recessive but appears dominant from the effect of the immune system, J VIROLOGY, 74(13), 2000, pp. 6193-6197
Fv-4 is a mouse gene that dominantly confers resistance to infection with F
riend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-4
78, 1975). However, the resistance caused by Fv-4 is recessive in nude mice
, which suggests that immunological effects play important roles in this re
sistance in vivo (K. Higo, Y. Kubo, Y. Iwatani, T. One, M. Maeda, a Hiai, T
. Masuda, K. Kuribayashi, F. Zhang, T. Lamin, A. Adachi, and A. Ishimoto, J
. Virol. 71:750-754, 1997). To determine the immunological effect on the re
sistance in vivo, we infected immunologically immature newborn mice homozyg
ous (Fv-4(r/r)) and heterozygous (Fv-4(r/-)) for Fv-4. Although the Fv-4(r/
r) mice showed complete resistance to F-MuLV whether infected neonatally or
as adolescents, the Fv-4(r/-) mice showed high sensitivity to viral prolif
eration and disease induction when infected as newborns but complete resist
ance when infected as adolescent mice. To confirm the immunological effect
on the resistance in adolescent mice with the Fv-4(r/r) and Fv-4(r/-) genot
ypes, we examined the effect of an immunosuppressant drug, FK506, on the re
sistance. The mice with the Fv-4(r/r) genotype treated with FK506 still sho
wed resistance, but the mice with the Fv-4(r/-) genotype became highly sens
itive to F-MuLV infection. Flow cytometric analysis to detect the Fv-4 gene
product showed that the Fv-4 gene product was expressed on the cells from
newborn and adolescent mice. The Fv-4 gene product was also detected on the
cells from the FK506-treated mice as well as on those from untreated mice.
However, a quantitative difference in the gene product between the cells w
ith the FV-4(r/r) and Fv-4(r/-) genotypes was detected by indirect staining
for how cytometry. These results show that the resistance to F-MuLV infect
ion conferred by the Fv-4 gene is originally recessive, but it looks domina
nt in adolescent mice mainly because of the effect of the immune system.