Resistance to Friend Murine Leukemia Virus Infection Conferred by the Fv-4 Gene Is Recessive but Appears Dominant from the Effect of the Immune System

Author:

Zhang Fengmin12,Ya Lamin Ta1,Iwatani Yasumasa1,Higo Kyoko1,Suzuki Yasunori1,Tanaka Masakazu1,Nakahara Tomomi1,Ono Takeshi1,Sakai Hiroyuki1,Kuribayashi Kagemasa3,Ishimoto Akinori1

Affiliation:

1. Laboratory of Gene Analysis, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507,1 and

2. Department of Microbiology, Harbin Medical University, Harbin 150086, People's Republic of China2

3. Department of Bioregulation, School of Medicine, Mie University, Tsu, Mie 514-8507,3 Japan, and

Abstract

ABSTRACT 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). However, the resistance caused by Fv-4 is recessive in nude mice, which suggests that immunological effects play important roles in this resistance in vivo (K. Higo, Y. Kubo, Y. Iwatani, T. Ono, M. Maeda, H. 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 resistance in vivo, we infected immunologically immature newborn mice homozygous ( 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 proliferation and disease induction when infected as newborns but complete resistance 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/− genotypes, we examined the effect of an immunosuppressant drug, FK506, on the resistance. The mice with the Fv-4 r/r genotype treated with FK506 still showed resistance, but the mice with the Fv-4 r/− genotype became highly sensitive 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 with the Fv-4 r/r and Fv-4 r/− genotypes was detected by indirect staining for flow cytometry. These results show that the resistance to F-MuLV infection conferred by the Fv-4 gene is originally recessive, but it looks dominant in adolescent mice mainly because of the effect of the immune system.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference32 articles.

1. Positional cloning of the mouse retrovirus restriction gene Fv1;Best S.;Nature,1996

2. Host genetic control of spontaneous and induced immunity to Friend murine retrovirus infection;Chesebro B.;Annu. Rev. Immunol.,1990

3. Rfv-1 and Rfv-2, two H-2-associated genes that influence recovery from Friend leukemia virus-induced splenomegaly;Chesebro B.;J. Immunol.,1978

4. Antibody-induced modulation of Friend virus cell surface antigens decreases virus production by persistent erythroleukemia cells: influence of the Rfv-3 gene;Chesebro B.;Proc. Natl. Acad. Sci. USA,1979

5. Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia;Friend C.;J. Exp. Med.,1956

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