The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five highly related envelope subgroups (A to E) thought to have evolved from a common viral ancestor in the chicken population. Three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup A to E ASLVs. Some inbred lines of chickens display phenotypes that are somewhere in between either efficiently susceptible or resistant to infection by specific subgroups of ASLV. The tvb gene encodes the receptor for subgroups B, D, and E ASLVs. The wild-type Tvb(S1) receptor confers susceptibility to subgroups B, D, and E ASLVs. In this study, the genetic defect that accounts for the altered susceptibility of an inbred chicken line, line M, to infection by ASLV(B), ASLV(D), and ASLV(E) was identified. The tvb gene in line M, tvb(r2), encodes a mutant Tvb(S1) receptor protein with a substitution of a serine for a cysteine at position 125 (C125S). Here, we show that the C125S substitution in Tvb(S1) significantly reduces the susceptibility of line M cells to infection by ASLV(B) and ASLV(D) and virtually eliminates susceptibility to ASLV(E) infection both in cultured cells and in the incidence and growth of avian sarcoma virus-induced sarcomas in chickens. The C125S substitution significantly reduces the binding affinity of the Tvb(S1) receptor for the subgroup B, D, and E ASLV envelope glycoproteins. These are the first results that demonstrate a possible role of the cysteine-rich domain 3 in the function of the Tvb receptors.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Vídenská 1083 CZ 14220 Prague 4 Czech Republic

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Adkins, H. B., S. C. Blacklow, and J. A. T. Young. 2001. Two functionally distinct forms of a retroviral receptor explain the nonreciprical receptor interference among subgroups B, D, and E avian leukosis viruses. J. Virol. 753520-3526. PubMed PMC

Adkins, H. B., J. Brojatsch, J. Naughton, M. M. Rolls, J. M. Pesola, and J. A. T. Young. 1997. Identification of a cellular receptor for subgroup E avian leukosis virus. Proc. Natl. Acad. Sci. USA 9411617-11622. PubMed PMC

Adkins, H. B., J. Brojatsch, and J. A. T. Young. 2000. Identification and characterization of a shared TNFR-related receptor for subgroup B, D and E avian leukosis viruses reveal cysteine residues required specifically for subgroup E viral entry. J. Virol. 743572-3578. PubMed PMC

Barnard, R. J., D. Elleder, and J. A. T. Young. 2006. Avian sarcoma and leukosis virus-receptor interactions: from classical genetics to novel insights into virus-cell membrane fusion. Virology 34425-29. PubMed

Barnard, R. J., and J. A. T. Young. 2003. Alpharetrovirus envelope-receptor interactions. Curr. Top. Microbiol. Immunol. 281107-136. PubMed

Bates, P., J. A. T. Young, and H. E. Varmus. 1993. A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor. Cell 741043-1051. PubMed

Brojatsch, J., J. Naughton, M. M. Rolls, K. Zingler, and J. A. T. Young. 1996. CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis. Cell 87845-855. PubMed

Crittenden, L. B., S. McMahon, M. S. Halpern, and A. M. Fadley. 1987. Embryonic infection with the endogenous avian leukosis virus Rous-associated virus-0 alters resposes to exogenous avian leukosis virus infection. J. Virol. 61722-725. PubMed PMC

Earp, L. J., S. E. Delos, H. E. Park, and J. M. White. 2005. The many mechanisms of viral membrane fusion proteins. Curr. Top. Microbiol. Immunol. 28525-66. PubMed PMC

Elleder, D., D. C. Melder, K. Trejbalová, J. Svoboda, and M. J. Federspiel. 2004. Two different molecular defects in the Tva receptor gene explain the resistance of two tvar lines of chickens to infection by subgroup A avian sarcoma and leukosis viruses. J. Virol. 7813489-13500. PubMed PMC

Elleder, D., V. Stepanets, D. C. Melder, F. Šenigl, J. Geryk, P. Pajer, J. Plachý, J. Hejnar, J. Svoboda, and M. J. Federspiel. 2005. The receptor for the subgroup C avian sarcoma and leukosis viruses, Tvc, is related to mammalian butrophilins, members of the immunoglobulin superfamily. J. Virol. 7910408-10419. PubMed PMC

Federspiel, M. J., and S. H. Hughes. 1997. Retroviral gene delivery. Methods Cell Biol. 52179-214. PubMed

Himly, M., D. N. Foster, I. Bottoli, J. S. Iacovoni, and P. K. Vogt. 1998. The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses. Virology 248295-304. PubMed

Hughes, S. H. 2004. The RCAS vector system. Folia Biol. 50107-119. PubMed

Hunter, E. 1997. Viral entry and receptors., p. 71-120. In J. M. Coffin, S. H. Hughes, and H. E. Varmus (ed.), Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. PubMed

Hymowitz, S. G., H. W. Christinger, G. Fuh, M. Ultsch, M. O'Connell, R. F. Kelley, A. Ashkenazi, and A. de Vos. 1999. Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Mol. Cell 4563-571. PubMed

Klucking, S., H. B. Adkins, and J. A. T. Young. 2002. Resistance of infection by subgroups B, D and E avian sarcoma and leukosis viruses is explained by a premature stop codon within a resistance allele of the tvb receptor gene. J. Virol. 767918-7921. PubMed PMC

Klucking, S., and J. A. T. Young. 2004. Amino acid residues Tyr-67, Asn-72, and Asp-73 of the Tvb receptor are important for subgroup E avian sarcoma and leukosis virus interaction. Virology 318371-380. PubMed

Knauss, D. J., and J. A. T. Young. 2002. A Fifteen-amino-acid Tvb peptide serves as a minimal soluble receptor for subgroup B avian leukosis and sarcoma viruses. J. Virol. 765404-5410. PubMed PMC

Murphy, H. M. 1977. A new, replication-defective variant of the Bryan high-titer strain Rous sarcoma virus. Virology 77705-721. PubMed

Plachý, J. 2000. The chicken—a laboratory animal of the class Aves. Folia Biol. 4617-24. PubMed

Plachý, J., J. Hejnar, K. Trtková, K. Trejbalová, J. Svoboda, and K. Hála. 2001. DNA vaccination against v-src oncogene-induced tumors in congenic chickens. Vaccine 194526-4535. PubMed

Ponten, J. 1964. The in vivo growth mechanism of avian Rous sarcoma. Natl. Cancer Inst. Monogr. 17131-145.

Reiche, E. M., A. M. Bonametti, J. C. Voltarelli, H. K. Morimoto, and M. A. Watanabe. 2007. Genetic polymorphisms in the chemokine and chemokine receptors: impact on clinical course and therapy of the human immunodeficiency virus type 1 infection. Curr. Med. Chem. 141325-1334. PubMed

Weiss, R. A. 1992. Cellular receptors and viral glycoproteins involved in retrovirus entry, p. 1-108. In J. A. Levy (ed.), The retroviruses, vol. 2. Plenum Press, New York, NY.

Young, J. A. T., P. Bates, and H. E. Varmus. 1993. Isolation of a chicken gene that confers susceptibility to infection by subgroup A avian leukosis and sarcoma viruses. J. Virol. 671811-1816. PubMed PMC

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