Subgroup J avian leukosis virus (ALV-J) is unique among the avian sarcoma and leukosis viruses in using the multimembrane-spanning cell surface protein Na(+)/H(+) exchanger type 1 (NHE1) as a receptor. The precise localization of amino acids critical for NHE1 receptor activity is key in understanding the virus-receptor interaction and potential interference with virus entry. Because no resistant chicken lines have been described until now, we compared the NHE1 amino acid sequences from permissive and resistant galliform species. In all resistant species, the deletion or substitution of W38 within the first extracellular loop was observed either alone or in the presence of other incidental amino acid changes. Using the ectopic expression of wild-type or mutated chicken NHE1 in resistant cells and infection with a reporter recombinant retrovirus of subgroup J specificity, we studied the effect of individual mutations on the NHE1 receptor capacity. We suggest that the absence of W38 abrogates binding of the subgroup J envelope glycoprotein to ALV-J-resistant cells. Altogether, we describe the functional importance of W38 for virus entry and conclude that natural polymorphisms in NHE1 can be a source of host resistance to ALV-J.

Department of Cellular and Viral Genetics Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague Czech Republic

Zobrazit více v PubMed

Barnard RJO, Elleder D, Young JAT. 2006. Avian sarcoma and leukosis virus-receptor interactions: from classical genetics to novel insights into virus-cell membrane vision. Virology 344:25–29 PubMed

Weiss RA. 1992. Cellular receptors and viral glycoproteins involved in retrovirus entry, p 1–108 Levy JA. (ed), Retroviridae, vol 2 Plenum Press, New York, NY

Bates P, Young JAT, Varmus HE. 1993. A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor. Cell 74:1043–1051 PubMed

Young JAT, Bates P, Varmus HE. 1993. Isolation of a chicken gene that confers susceptibility to infection by subgroup A avian leukosis and sarcoma viruses. J. Virol. 67:1811–1816 PubMed PMC

Adkins HB, Brojatsch J, Naughton J, Rolls MM, Pesola JM, Young JAT. 1997. Identification of a cellular receptor for subgroup E avian leukosis virus. Proc. Natl. Acad. Sci. U. S. A. 94:11617–11622 PubMed PMC

Adkins HB, Brojatsch J, Young JAT. 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. 74:3572–3578 PubMed PMC

Brojatsch J, Naughton J, Rolls MM, Zingler K, Young JA. 1996. CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis. Cell 87:845–855 PubMed

Elleder D, Stepanets V, Melder DC, Šenigl F, Geryk J, Pajer P, Plachý J, Hejnar J, Svoboda J, Federspiel MJ. 2005. The receptor for the subgroup C avian sarcoma and leukosis viruses, Tvc, is related to mammalian butyrophilins, members of the immunoglobulin superfamily. J. Virol. 79:10408–10419 PubMed PMC

Elleder D, Melder DC, Trejbalová K, Svoboda J, Federspiel MJ. 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. 78:13489–13500 PubMed PMC

Klucking S, Adkins HB, Young JAT. 2002. Resistance to 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. 76:7918–7921 PubMed PMC

Reinišová M, Plachý J, Trejbalová K, Šenigl F, Kučerová D, Geryk J, Svoboda J, Hejnar J. 2012. Intronic deletions that disrupt mRNA splicing of the tva receptor gene result in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroup A. J. Virol. 86:2021–2030 PubMed PMC

Reinišová M, Šenigl F, Yin X, Plachý J, Geryk J, Elleder D, Svoboda J, Federspiel MJ, Hejnar J. 2008. A single-amino-acid substitution in the TvbS1 receptor results in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroups B and D and resistance to infection by subgroup E in vitro and in vivo. J. Virol. 82:2097–2105 PubMed PMC

Payne LN, Brown SR, Bumstead N, Howes K, Frazier JA, Thouless ME. 1991. A novel subgroup of exogenous avian leukosis virus in chickens. J. Gen. Virol. 72:801–807 PubMed

Payne LN, Gillespie AM, Howes K. 1992. Myeloid leukaemogenicity and transmission of the HPRS103 strain of avian leukosis virus. Leukemia 6:1167–1176 PubMed

Payne LN, Nair V. 2012. The long view: 40 years of avian leukosis research. Avian Pathol. 41:11–19 PubMed

Payne LN, Howes K, Gillespie AM, Smith LM. 1992. Host range of Rous sarcoma virus pseudotype RSV(HPRS103) in 12 avian species: support of a new avian retrovirus subgroup, designated J. J. Gen. Virol. 73:2995–2997 PubMed

Bai J, Howes K, Payne LN, Skinner MA. 1995. Sequence of host-range determinants in the env gene of a full-length infectious proviral clone of exogenous avian leukosis virus HPRS-103 confirms that it represents a new subgroup (designated J). J. Gen. Virol. 76:181–187 PubMed

Benson SJ, Ruis BL, Fadly AM, Conklin KF. 1998. The unique envelope gene of the subgroup J avian leukosis virus derives from ev/J proviruses, a novel family of avian endogenous viruses. J. Virol. 72:10157–10164 PubMed PMC

Chai N, Bates P. 2006. Na+/H+ exchanger type 1 is a receptor for pathogenic subgroup J avian leukosis virus. Proc. Natl. Acad. Sci. U. S. A. 103:5531–5536 PubMed PMC

Hunt HD, Lee LF, Foster D, Silva RF, Fadly AM. 1999. A genetically engineered cell line resistant to subgroup J avian leukosis virus infection (C/J). Virology 264:205–210 PubMed

Gao Y, Yun B, Qin L, Pan W, Qu Y, Liu Z, Wang Y, Qi X, Gao H, Wang X. 2012. Molecular epidemiology of avian leukosis virus subgroup J in layer flocks in China. J. Clin. Microbiol. 50:953–960 PubMed PMC

Klucking S, Young JAT. 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 318:371–380 PubMed

Knauss DJ, Young JAT. 2002. A fifteen-amino-acid TVB peptide serves as a minimal soluble receptor for subgroup B avian leukosis and sarcoma viruses. J. Virol. 76:5404–5410 PubMed PMC

Munguia A, Federspiel MJ. 2008. Efficient subgroup C avian sarcoma and leukosis virus receptor activity requires the IgV domain of the Tvc receptor and proper display on the cell membrane. J. Virol. 82:11419–11428 PubMed PMC

Federspiel MJ, Hughes SH. 1997. Retroviral gene delivery. Methods Cell Biol. 52:167–177 PubMed

Hughes SH. 2004. The RCAS vector system. Folia Biol. (Praha) 50:107–119 PubMed

Plachý J. 2000. The chicken—a laboratory animal of the class Aves. Folia Biol. (Praha) 46:17–24 PubMed

Nehyba J, Svoboda J, Karakoz I, Geryk J, Hejnar J. 1990. Ducks, a new experimental host system for studying persistent infection with avian leukaemia retroviruses. J. Gen. Virol. 71:1937–1945 PubMed

Himly M, Foster DN, Bottoli I, Iacovoni JS, Vogt PK. 1998. The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses. Virology 248:295–304 PubMed

Moscovici C, Moscovici MG, Jimenez H, Lai MM, Hayman MJ, Vogt PK. 1977. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell 11:95–103 PubMed

Šenigl F, Auxt M, Hejnar J. 2012. Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site. Nucleic Acids Res. 40:5298–5312 PubMed PMC

Plachý J, Hejnar J, Trtková K, Trejbalová K, Svoboda J, Hála K. 2001. DNA vaccination against v-src oncogene-induced tumours in congenic chickens. Vaccine 19:4526–4535 PubMed

Chesters PM, Howes K, Petherbridge L, Evans S, Payne LN, Venugopal K. 2002. The viral envelope is a major determinant for the induction of lymphoid and myeloid tumours by avian leukosis virus subgroups A and J, respectively. J. Gen. Virol. 83:2553–2561 PubMed

Malhotra S, Scott AG, Zavorotinskaya T, Albritton LM. 1996. Analysis of the murine ecotropic leukemia virus receptor reveals a common biochemical determinant on diverse cell surface receptors that is essential to retrovirus entry. J. Virol. 70:321–326 PubMed PMC

Rong L, Gendron K, Strohl B, Shenoy R, Wool-Lewis RJ, Bates P. 1998. Characterization of determinants for envelope binding and infection in Tva, the subgroup A avian sarcoma and leukosis virus receptor. J. Virol. 72:4552–4559 PubMed PMC

Wyatt R, Kwong PD, Desjardins E, Sweet RW, Robinson J, Hendrickson WA, Sodroski JG. 1998. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393:705–711 PubMed

Kozak CA. 2011. Naturally occurring polymorphisms of the mouse gammaretrovirus receptors CAT-1 and XPR1 alter virus tropism and pathogenicity. Adv. Virol. 2011:e975801.10.1155/2011/975801 PubMed DOI PMC

Kemp G, Young H, Fliegel L. 2008. Structure and function of the human Na+/H+ exchanger isoform 1. Channels 5:329–336 PubMed

Borgese F, Sardet C, Cappadoro M, Pouyssegur J, Motais R. 1992. Cloning and expression of a cAMP-activated Na+/H+ exchanger: evidence that the cytoplasmic domain mediates hormonal regulation. Proc. Natl. Acad. Sci. U. S. A. 89:6765–6769 PubMed PMC

Denker SP, Barber DL. 2002. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J. Cell Biol. 159:1087–1096 PubMed PMC

Cardone RA, Casavola V, Reshkin SH. 2005. The role of disturbed pH dynamics and the Na+H+ exchanger in metastasis. Nat. Rev. Cancer 5:786–795 PubMed

Ruis BL, Benson SJ, Conklin KF. 1999. Genome structure and expression of the ev/J family of avian endogenous viruses. J. Virol. 73:5345–5355 PubMed PMC

Denesvre C, Soubieux D, Pin G, Hue D, Dambrine G. 2003. Interference between avian endogenous ev/J 4.1 and exogenous ALV-J retroviral envelopes. J. Gen. Virol. 84:3233–3238 PubMed

Bolisetty M, Blomberg J, Benachenhou F, Sperber G, Beemon K. 2012. Unexpected diversity and expression of avian endogenous retroviruses. mBio 3(5):e00344–12.10.1128/mBio.00344-12 PubMed DOI PMC

Ikeda H, Sugimura H. 1989. Fv-4 resistance gene: a truncated endogenous murine leukemia virus with ecotropic interference properties. J. Virol. 63:5405–5412 PubMed PMC

Lyu MS, Nihrane A, Kozak CA. 1999. Receptor-mediated interference mechanism responsible for resistance to polytropic leukemia retroviruses in Mus castaneus. J. Virol. 73:3733–3736 PubMed PMC

Adkins HB, Blacklow SC, Young JAT. 2001. Two functionally distinct forms of a retroviral receptor explain the nonreciprocal receptor interference among subgroup B, D, and E avian leukosis viruses. J. Virol. 75:3520–3526 PubMed PMC

Rapid adaptive evolution of avian leukosis virus subgroup J in response to biotechnologically induced host resistance

Independent loss events of a functional tetherin gene in galliform birds

Knock-Out of Retrovirus Receptor Gene Tva in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B12)-Dependent Level of Methylmalonic Acid

Precise CRISPR/Cas9 editing of the NHE1 gene renders chickens resistant to the J subgroup of avian leukosis virus

The Current View of Retroviruses as Seen from the Shoulders of a Giant

The Novel Avian Leukosis Virus Subgroup K Shares Its Cellular Receptor with Subgroup A

Genetic Resistance to Avian Leukosis Viruses Induced by CRISPR/Cas9 Editing of Specific Receptor Genes in Chicken Cells

Identification of New World Quails Susceptible to Infection with Avian Leukosis Virus Subgroup J

Genetic Diversity of NHE1, Receptor for Subgroup J Avian Leukosis Virus, in Domestic Chicken and Wild Anseriform Species