The first step in poliovirus replication is binding of virus to a cellular receptor. Mouse L cells, which are resistant to poliovirus infection because they do not bear a poliovirus receptor, were transformed with HeLa cell (human) DNA to poliovirus sensitivity at a frequency of 1 in 50,000 transformants. Monoclonal antibody directed against the HeLa cell poliovirus receptor site was used in rosette assays to identify poliovirus-sensitive L-cell transformants in a background of L-cell tk' transformants. A cloned cell line, CM-1, was isolated that displayed a surface component recognized by the antipoliovirus receptor antibody. CM-1 cells were susceptible to infection with all three poliovirus serotypes, and infection could be blocked by the antireceptor antibody. Poliovirus formed plaques in CM-1 and HeLa cells with equal efficiency. CM-1 and HeLa cells produced infectious poliovirus at a similar rate, although yield of virus in CM-1 cells was about 33% less than the yield in HeLa cells. These results suggest that DNA encoding the HeLa cell poliovirus receptor has been introduced into mouse cells, resulting in the expression of the receptor and susceptibility to poliovirus infection.Poliovirus is an icosahedral RNA-containing virus with a host range that is limited to primates and primate cell cultures. In the infected host, viral replication occurs predominantly in the intestinal mucosa, in certain lymphoid tissue, and in the central nervous system (1). A large body of evidence indicates that a cellular receptor is the major determining factor in cell and tissue susceptibility to poliovirus infection (reviewed in ref. 2). This conclusion is supported by the observation that bypassing the receptor binding step by transfection of cells with RNA permits one cycle of replication in many receptor-negative mammalian cell types (3). A complete understanding of poliovirus replication and pathogenesis therefore requires better knowledge of the structure, function, and expression of the viral receptor that plays an important role in cell and tissue tropism.Early studies showed that tissues and cell types that are susceptible to poliovirus infection contain a membraneassociated activity that is capable of specifically binding poliovirus (4)(5)(6). Subsequent studies have shown that the virus binding activity, or receptor, is an integral membrane protein (7,8). There are -3000 receptor sites on the HeLa cell membrane, but it is not known how many receptors comprise a binding site (9). The three poliovirus serotypes compete for a binding site that is distinct from that of other enteroviruses (10-13). Recently, a receptor protein from coxsackievirus B3, an enterovirus related to poliovirus, was purified from HeLa cells (14). Attempts to isolate and characterize the poliovirus receptor have not been successful, probably because there are so few receptors per cell and because so far it has not been possible to measure virus binding activity in the presence of detergents (7).To circumvent the difficulties associated wit...