Na+/H+ exchanger type 1 is a receptor for pathogenic subgroup J avian leukosis virus.
Subgroup J avian leukosis virus (ALV-J) is a recently identified avian oncogenic retrovirus responsible for severe economic losses worldwide. In contrast with the other ALV subgroups, ALV-J predominantly induces myeloid leukosis in meat-type chickens. Despite significant homology with the other ALV subgroups across most of the genome, the envelope protein of ALV-J (EnvJ) shares low homology with the others. Pathogenicity and myeloid leukosis induction map to the env gene of ALV-J. A chimeric protein composed of the surface domain of EnvJ fused to the constant region of a rabbit IgG and mass spectrometry were used to identify the chicken Na(+)/H(+) exchanger type 1 (chNHE1) as a binding protein for ALV-J. Flow cytometry analysis and coprecipitation experiments demonstrated a specific interaction between EnvJ and chNHE1. When introduced into nonpermissive human 293T cells and quail QT6 cells, chNHE1 conferred susceptibility to EnvJ-mediated infection. Furthermore, 293T cells expressing chNHE1 fused with 293T cells expressing EnvJ in a low-pH-dependent manner. Together, these data identify chNHE1 as a cellular receptor for the highly pathogenic ALV-J.
Department of Microbiology, University of Pennsylvania School of Medicine, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
Ning
N
Chai
Paul
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Bates
D000595:Amino Acid Sequence; D000818:Animals; D001354:Avian Leukosis Virus / Q000502:physiology*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000502:physiology*; D002459:Cell Fusion; D002460:Cell Line; D002645:Chickens; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D011784:Quail; D011991:Receptors, Virus / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000502:physiology*
D027682:Cation Transport Proteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers