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Gene Review

Fv4  -  Friend virus susceptibility 4

Mus musculus

Synonyms: Akvr-1, Env, Fv-4, Retrovirus-related Env polyprotein from Fv-4 locus
 
 
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Disease relevance of Fv4

  • This study identifies an Rmcf-linked MCF provirus and indicates that, like the ecotropic virus resistance gene Fv4, Rmcf may mediate resistance through an interference mechanism [1].
  • Friend murine leukemia virus resistance in Japanese wild mice: possible allelism with Fv-4 in FRG mice [2].
  • METHODS:: HIV Env and Gag immunogens derived from Thailand B (B'), C/B' recombinant and A/E recombinant were selected as these three clades account for 29%, 45% and 15% of HIV-1 prevalence in China, respectively [3].
  • Fv-4 is a mouse gene that confers resistance to infection with ecotropic retroviruses [4].
  • Construction and characterization of the recombinant Moloney murine leukemia viruses bearing the mouse Fv-4 env gene [5].
 

High impact information on Fv4

  • [(C4W X DBA/2) X C57BL/6-Fvs] crosses revealed that Fv-4wr is located on chromosome 12 with the gene order of Fv-4w-Pre-1-lgh-1, apparently at the same site as the Fv-4 [6].
  • The membrane fusion activity of murine leukaemia virus Env is carried by the transmembrane (TM) and controlled by the peripheral (SU) subunit [7].
  • These results suggest that Env is stabilized by Ca(2+) and that receptor binding triggers a cascade of reactions involving Ca(2+) removal, CXXC-thiol exposure, SU-TM disulphide-bond isomerization and SU dissociation, which lead to fusion activation [7].
  • A unique sequence related to the ecotropic murine leukemia virus is associated with the Fv-4 resistance gene [8].
  • The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env-expressing vaccinia virus [9].
 

Chemical compound and disease context of Fv4

  • Retrovirus entry into cells is mediated by specific interactions between the retrovirally encoded Env envelope glycoprotein and a host cell surface receptor [10].
  • This occurs only in the situation in which the incorporated MuLV-Env protein has been activated to fusion activity by HIV protease-mediated removal of the C-terminal R-peptide and is completely inhibited when the respective particles are generated in the presence of the HIV protease inhibitor, Saquinavir [11].
  • Proliferative or cytotoxic T-cell responses against several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral immunization with BCG expressing these proteins [12].
 

Biological context of Fv4

  • The phenotype of recovery from viremia in Fv4-11 mice was unexpected and suggests that low levels of expression of the Fv-4 gene enhance the effectiveness of the immune response [4].
  • The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype [13].
  • 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 [14].
  • A nucleotide sequence of the mouse Fv-4 env gene was completed [5].
  • 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 [13].
 

Anatomical context of Fv4

  • Peptides spanning the entire Env and Gag were used as stimuli and Elispot assay was used to assess the T cell immunity [3].
  • Inhibition of murine AIDS (MAIDS), development by the transplantation of bone marrow cells carrying the Fv-4 resistance gene to MAIDS virus-infected mice [15].
  • The recombinant clone containing the Fv-4 AccI-EcoRV region, i.e., almost the entire Fv-4 env sequence, was introduced with pSV2neo into NIH 3T3 cells, and a G418r cell line named NIH(Fv4)-2 was isolated [5].
  • 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 [14].
  • A cell membrane "gp70" associated with Fv-4 gene: immunological characterization, and tissue and strain distribution [16].
 

Associations of Fv4 with chemical compounds

  • This second novel virus resistance phenotype has been associated with expression of viral Env glycoprotein; Northern blotting with specific hybridization probes identified a spliced X-MLV env message unique to virus-resistant mice [17].
  • To investigate the role of this phosphorylation, Ser-16 was substituted with alanine or glutamic acid in full-length v-Mos (an Env-Mos fusion protein that contains 31 additional amino acids at the amino terminus of c-Mos), its mouse c-Mos equivalent version (v-Mos residues 32-374, hereafter referred to as Mos), and mouse c-Mos [18].
  • In contrast, we observed that the palmitoylation-deficient mutant Env protein was mostly soluble when extracted by ice-cold TX-100 and stayed at the bottom of the gradients [19].
  • Duplications and a deletion were found in a restricted region of the hypervariable proline-rich region of Env glycoprotein [20].
  • The resulting del3-mpl oncogene product conserves in its extracellular region the first 12 amino acids of the Env signal sequence including a cysteine residue, and 25 amino acids of the v-Mpl [21].
 

Regulatory relationships of Fv4

  • Fv4 is an endogenous defective murine leukaemia virus (MuLV) which expresses high levels of an envelope protein (Env) closely related to that of the ecotropic class of MuLVs [22].
 

Other interactions of Fv4

  • Genetic resistance to Friend leukemia virus in mice: masking of Fv-2 phenotype by an epistatic gene, Fv-4 [23].
  • Fv4 mice secrete the surface peptide (SU) of the Fv4 Env in their serum and this secreted Env can block infection of NIH3T3 cells [22].
 

Analytical, diagnostic and therapeutic context of Fv4

  • However, when the virus-infected mice were subjected to cobalt irradiation and then given an intravenous injection of 10(7) BALB/c-Fv-4wr mouse bone marrow cells, the recipient mice survived much longer than the untreated mice, which suggests that the Fv-4 gene is a dominant inhibitory gene that is potentially useful in gene therapy of MAIDS [15].
  • Transgenic mice were derived using the native Fv-4 gene as the construct for microinjection [24].
  • In the complement-dependent cytotoxicity test, the antiserum killed the hematopoietic cells derived from Fv-4r/- mice but not these from Fv-4s/s mice, and the genetic cross experiments located the locus controlling the expression of the target molecule of the antibody in the close vicinity of Fv-4 [25].
  • METHODS: Using surface plasmon resonance (SPR) measurement, the interaction was measured between recombinant soluble gp41 (rsgp41, Env aa539-684) and protein P62 [26].
  • An intranasal route of vaccination with VSV-Env also elicited a strong primary response to Env [27].

References

  1. Characterization of a polytropic murine leukemia virus proviral sequence associated with the virus resistance gene Rmcf of DBA/2 mice. Jung, Y.T., Lyu, M.S., Buckler-White, A., Kozak, C.A. J. Virol. (2002) [Pubmed]
  2. Friend murine leukemia virus resistance in Japanese wild mice: possible allelism with Fv-4 in FRG mice. Suzuki, S., Tsuji, K., Moriwaki, K. J. Natl. Cancer Inst. (1981) [Pubmed]
  3. Sequential priming and boosting with heterologous HIV immunogens predominantly stimulated T cell immunity against conserved epitopes. Xu, J., Ren, L., Huang, X., Qiu, C., Liu, Y., Liu, Y., Shao, Y. AIDS (2006) [Pubmed]
  4. Transgenic Fv-4 mice resistant to Friend virus. Limjoco, T.I., Dickie, P., Ikeda, H., Silver, J. J. Virol. (1993) [Pubmed]
  5. Construction and characterization of the recombinant Moloney murine leukemia viruses bearing the mouse Fv-4 env gene. Masuda, M., Yoshikura, H. J. Virol. (1990) [Pubmed]
  6. Fv-4: gene controlling resistance to NB-tropic Friend murine leukemia virus. Distribution in wild mice, introduction into genetic background of BALB/c mice, and mapping of chromosomes. Odaka, T., Ikeda, H., Yoshikura, H., Moriwaki, K., Suzuki, S. J. Natl. Cancer Inst. (1981) [Pubmed]
  7. Isomerization of the intersubunit disulphide-bond in Env controls retrovirus fusion. Wallin, M., Ekström, M., Garoff, H. EMBO J. (2004) [Pubmed]
  8. A unique sequence related to the ecotropic murine leukemia virus is associated with the Fv-4 resistance gene. Kozak, C.A., Gromet, N.J., Ikeda, H., Buckler, C.E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  9. Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env. Xin, K.Q., Hoshino, Y., Toda, Y., Igimi, S., Kojima, Y., Jounai, N., Ohba, K., Kushiro, A., Kiwaki, M., Hamajima, K., Klinman, D., Okuda, K. Blood (2003) [Pubmed]
  10. Efficient cell infection by Moloney murine leukemia virus-derived particles requires minimal amounts of envelope glycoprotein. Bachrach, E., Marin, M., Pelegrin, M., Karavanas, G., Piechaczyk, M. J. Virol. (2000) [Pubmed]
  11. Inter-retroviral fusion mediated by human immunodeficiency virus or murine leukemia virus glycoproteins: independence of cellular membranes and membrane vesicles. Sparacio, S., Pfeiffer, T., Holtkotte, D., Bosch, V. Virology (2002) [Pubmed]
  12. Oral immunization with recombinant BCG induces cellular and humoral immune responses against the foreign antigen. Lagranderie, M., Murray, A., Gicquel, B., Leclerc, C., Gheorghiu, M. Vaccine (1993) [Pubmed]
  13. Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection. Higo, K., Kubo, Y., Iwatani, Y., Ono, T., Maeda, M., Hiai, H., Masuda, T., Kuribayashi, K., Zhang, F., Lamin, T.Y., Adachi, A., Ishimoto, A. J. Virol. (1997) [Pubmed]
  14. 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. Zhang, F., Ya, L.T., Iwatani, Y., Higo, K., Suzuki, Y., Tanaka, M., Nakahara, T., Ono, T., Sakai, H., Kuribayashi, K., Ishimoto, A. J. Virol. (2000) [Pubmed]
  15. Inhibition of murine AIDS (MAIDS), development by the transplantation of bone marrow cells carrying the Fv-4 resistance gene to MAIDS virus-infected mice. Nakagawa, Y., Kakimi, K., Ling, W., Kubo, Y., Higo, K., Masuda, T., Kuribayashi, K., Iwashiro, M., Komatz, Y., Hirama, T. J. Virol. (1994) [Pubmed]
  16. A cell membrane "gp70" associated with Fv-4 gene: immunological characterization, and tissue and strain distribution. Ikeda, H., Odaka, T. Virology (1984) [Pubmed]
  17. Rmcf2, a xenotropic provirus in the Asian mouse species Mus castaneus, blocks infection by polytropic mouse gammaretroviruses. Wu, T., Yan, Y., Kozak, C.A. J. Virol. (2005) [Pubmed]
  18. Evidence for an important role of serine 16 and its phosphorylation in the stabilization of c-Mos. Pham, C.D., Vuyyuru, V.B., Yang, Y., Bai, W., Singh, B. Oncogene (1999) [Pubmed]
  19. Palmitoylation of the murine leukemia virus envelope protein is critical for lipid raft association and surface expression. Li, M., Yang, C., Tong, S., Weidmann, A., Compans, R.W. J. Virol. (2002) [Pubmed]
  20. Virological properties and nucleotide sequences of Cas-E-type endogenous ecotropic murine leukemia viruses in South Asian wild mice, Mus musculus castaneus. Ikeda, H., Kato, K., Kitani, H., Suzuki, T., Yoshida, T., Inaguma, Y., Yamamoto, N., Suh, J.G., Hyun, B.H., Yamagata, T., Namikawa, T., Tomita, T. J. Virol. (2001) [Pubmed]
  21. Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization. Courtois, G., Bénit, L., Mikaeloff, Y., Pauchard, M., Charon, M., Varlet, P., Gisselbrecht, S. J. Virol. (1995) [Pubmed]
  22. Secretion of a murine retroviral Env associated with resistance to infection. Nihrane, A., Lebedeva, I., Lyu, M.S., Fujita, K., Silver, J. J. Gen. Virol. (1997) [Pubmed]
  23. Genetic resistance to Friend leukemia virus in mice: masking of Fv-2 phenotype by an epistatic gene, Fv-4. Odaka, T., Ikeda, H. Jpn. J. Exp. Med. (1977) [Pubmed]
  24. Resistance to Friend leukemia virus in transgenic mice expressing the native Fv-4 gene. Jackson, M.K., Mitchell, E.A., Winslow, S.G., Okelberry, K.M., Sidwell, R.W., Morrey, J.D. Acta Virol. (1999) [Pubmed]
  25. Surface antigen expressed in hematopoietic cells derived from Fv-4r mouse strains. Yoshikura, H., Odaka, T. J. Natl. Cancer Inst. (1982) [Pubmed]
  26. The C domain of HIV-1 gp41 binds the putative cellular receptor protein P62. Chen, Y.H., Xiao, Y., Wu, W., Yang, J., Sui, S., Dierich, M.P. AIDS (1999) [Pubmed]
  27. High-level primary CD8(+) T-cell response to human immunodeficiency virus type 1 gag and env generated by vaccination with recombinant vesicular stomatitis viruses. Haglund, K., Leiner, I., Kerksiek, K., Buonocore, L., Pamer, E., Rose, J.K. J. Virol. (2002) [Pubmed]
 
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