Human Cytomegalovirus Escapes a Naturally Occurring Neutralizing Antibody by Incorporating It into Assembling Virions

摘要: Human cytomegalovirus (CMV) is a common but difficult to treat infection of immunocompromised patients. MSL-109 human monoclonal IgG isolated from CMV seropositive individual that recognizes the viral glycoprotein H (gH) surface antigen complexes mediate entry. Although blocks in vitro, it lacked sufficient efficacy in trials, and treated patients suggested evolution resistance. To understand how escapes MSL-109, we characterized MSL-109-resistant strain. Our results elucidate nongenetic escape mechanism which antibody selectively taken up by infected cells incorporated into assembling virions dose-dependent manner. The resistant virus then utilizes Fc domain infect naive nonimmune cells. This resistance may explain clinical failure illustrate general escape, inform antiviral vaccine therapeutic development.