SUMMARYHuman sera containing respiratory syncytial (RS) virus-specific antibodies enhance RS virus infection of the U937 macrophage cell line. There was an increase in the number of cells expressing virus antigen when U937 cells were infected with RS virus in the presence of human serum compared to cells infected in the absence of human serum. Human sera enhanced virus yield, as measured by the cell-released infectious virus, by an average of 50-fold compared to virus infection in the absence of human serum. The comparison of the enhancing activities of paired acute and convalescent human sera showed that the titre of enhancing antibody increased in parallel with the titre of RS virus-specific antibody measured by complement fixation and virus neutralization. An RS virus-specific neutralizing monoclonal antibody directed to the virus F protein enhanced virus infection of U937 cells. A non-neutralizing monoclonal antibody directed to the virus nucleoprotein did not enhance virus infection. The possible role of enhancing antibodies in vivo is discussed.
INTRODUCTIONRespiratory syncytial (RS) virus is a major cause of acute respiratory infections in young children. The use of a formalin-inactivated RS virus vaccine predisposed children to severe illness when subsequently infected with RS virus (Kim et al., 1969). Following immunization, children developed lower neutralizing antibody titres than those of a comparable age who had natural RS virus infections and had not been immunized (Murphy et al., 1986). Chin et al. (1969) found higher virus shedding and virus isolation rates in vaccinees compared to unvaccinated children when both groups were naturally infected with RS virus. These data led to the speculation that low antibody titres contributed to the severity of the RS virus infections. A possible explanation for these data is antibody-dependent enhancement of virus infection, as proposed by Porterfield (1982) and Halstead (1982), although no experimental data were presented at that time.The in vitro enhancement of virus infection of macrophage cell lines by virus-specific antibodies at sub-neutralizing concentrations has been reported for several viruses (reviewed by Halstead, 1982). The initial stages of virus enhancement require the formation of a virusantibody complex which then attaches, via the Fc portion of the antibody, to the macrophage Fc receptor; this facilitates the entry of the virus as compared to virus infection in the absence of antibody (Gollins & Porterfield, 1984). The sites of replication of RS virus in the respiratory tract are poorly understood and the role of antibody-dependent enhancement in RS virus pathogenesis remains to be determined. Recently, RS virus has been shown to replicate in vitro in human peripheral blood mononuclear leukocytes (Krilov et al., 1987). In addition, RS virus antigen has been found in circulating mononuclear leukocytes of infants with RS virus infections (Dumorat et al., 1985). The present report describes the infection of the U937 human macrophage cell line by...