Human cytomegalovirus infection elicits a glycoprotein M (gM)/gN-specific virus-neutralizing antibody response.
Human cytomegalovirus (HCMV) is a ubiquitous human pathogen that infects 40 to 90% of adult human populations. HCMV infections are often asymptomatic in healthy individuals but can cause severe organ and life-threatening disease in immunocompromised patients. The antiviral antibody response to HCMV infection is complex and is known to include virus-neutralizing antibody production against surface glycoproteins encoded by HCMV. We have investigated the human antibody response to a complex of HCMV surface glycoproteins composed of glycoprotein M (gM)/gN, the gene products of the UL100 and UL73 open reading frames. Mouse monoclonal antibodies generated against gM/gN have previously been shown to neutralize HCMV infection of human fibroblasts in vitro. To determine whether human antibodies reactive with the gM/gN complex possess virus-neutralizing properties, we isolated human antibodies reactive with gM/gN from pooled human HCMV hyperimmune globulin by affinity purification using recombinant gM/gN. The affinity-purified human anti-gM/gN antibodies reacted specifically by immunofluorescence with HCMV-infected human fibroblasts and with cells transiently expressing gM/gN, but not with cells transfected with plasmids encoding other immunogenic HCMV proteins. The anti-gM/gN antibodies also reacted specifically only with gM/gN in immunoblot assays using lysates of transfected cells expressing specific HCMV proteins. Last, human anti-gM/gN antibodies efficiently neutralized infectious HCMV in vitro with a capacity comparable to that of human anti-gB antibodies. These data indicated that gM/gN can elicit a virus-neutralizing antibody response in humans infected with HCMV and therefore should be considered a potential candidate for inclusion in prophylactic CMV vaccines.
Shimamura
Masako
M
Department of Pediatrics, University of Alabama at Birmingham, 1600 6th Avenue South, CHB107, Birmingham, Alabama 35233, USA.
Mach
Michael
M
Britt
William J
WJ
D000042:Absorption; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D014771:Virion / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; C417883:glycoprotein N, Human cytomegalovirus