Complex formation by human cytomegalovirus glycoproteins M (gpUL100) and N (gpUL73).
The envelope glycoproteins of human cytomegalovirus (HCMV) virions are incompletely characterized. We have analyzed complex formation between glycoprotein M (gM or gpUL100) and a second glycoprotein. gM-homologous proteins are conserved throughout the herpesvirus family and represent type III membrane proteins containing multiple hydrophobic sequences. In extracellular HCMV particles, gM was found to be complexed through disulfide bonds to a second protein with an apparent molecular mass of 50 to 60 kDa. The 50- to 60-kDa protein was found to be derived from reading frame UL73 of HCMV strain AD169. UL73-homologous genes are also conserved within herpesviruses. When transiently expressed by itself, the UL73 gene product consisted of a protein of 18 kDa. However, in the presence of gM, the UL73 gene product was posttranslationally modified to the 50- to 60-kDa species. Thus, gM and the UL73 gene product, which represents the gN homolog of herpesviruses, form a disulfide-linked complex in HCMV virions. Transient expression of gM and gN followed by fluorescence imaging with monoclonal antibodies against either protein demonstrated that complex formation was required for transport of the proteins from the endoplasmic reticulum to the Golgi and trans-Golgi compartments. Finally, we tested the gM-gN complex for reactivity with sera from HCMV-seropositive donors. Whereas most sera failed to react with either gM or gN when expressed alone, 62% of sera were positive for the gM-gN complex. Because a murine monoclonal antibody reactive with gN in the gM-gN complex efficiently neutralizes infectious virus, the gM-gN complex may represent a major antigenic target of antiviral antibody responses.
Mach
M
M
Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany. mlmach@viro.med.uni-erlangen.de
Kropff
B
B
Dal Monte
P
P
Britt
W
W
D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D011485:Protein Binding; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; C095281:UL100 protein, Cytomegalovirus; D014759:Viral Envelope Proteins; C417883:glycoprotein N, Human cytomegalovirus