THE RECEPTOR FOR THE SUBGROUP-A AVIAN LEUKOSIS-SARCOMA VIRUSES BINDS TO SUBGROUP-A BUT NOT TO SUBGROUP-C ENVELOPE GLYCOPROTEIN

The putative subgroup A avian leukosis-sarcoma virus (ALSV) receptor ( Tva) was recently cloned by gene transfer (P. Bates, J. A. Young, and Il. E. Varmus, Cell 74:1043-1051, 1993; J. A. T. Young, P. Bates, and H. E. Varmus, J. Virol. 67:1811-1816, 1993). Susceptibility to infecti on by subgroup A ALSV is conferred on cells upon transfection with cDN As encoding tva. The hypothesis that tva encodes a specific receptor f or subgroup A ALSV predicts that the Tva protein should bind to subgro up A, but not to subgroup C, envelope glycoprotein. In this study, we examined this prediction by using several biochemical assays. We estab lished stable NIH 3T3 cell lines expressing either Tva, the subgroup A envelope glycoprotein (Env-A), or the subgroup C envelope glycoprotei n (Env-C) and used them in conjunction with soluble forms of these mol ecules to demonstrate specific binding. When cell lysates containing T va were mixed with lysates of either Env-A or Env-C, an immunoprecipit able complex formed between Tva and Env A but not between Tva and Env- C. A soluble, oligomeric form of Env-A, not Env-C, binds to cells expr essing Tva. Reciprocally, a secreted form of Tva can bind to cells exp ressing Env-A but not to cells expressing Env-C. A specific and stable complex formed between soluble Env-A and secreted Tva as demonstrated by sucrose density gradient centrifugation. Thus, by three kinds of a ssays, Tva appears to bind specifically to Env-A, which is consistent with genetic evidence that it serves as the cell surface receptor of s ubgroup A ALSV and the main determinant of subgroup specificity.