Synthesis and processing of the major envelope glycoprotein of murine cytomegalovirus

Abstract

We have characterized the synthesis and processing pathway of the major envelope glycoprotein complex of murine cytomegalovirus (gp52/105/150). We have demonstrated that it belongs to the “late” kinetic class of MCMV proteins, and is initially synthesized as a 128K glycoprotein (gpl 28) which contains N-linked, high-mannose type oligosaccharide chains and is phosphorylated predominantly at serine residues. A fraction of the gp128 molecules also contains O-linked GaINAc residues. The majority of the gpl28 molecules appears to be retained in the endoplasmic reticulum as evidenced by their sensitivity to endoglycosidase H digestion. The formation of disulfide linkages and dimerization allow the transport of gpl28 to the Golgi compartments where modification of N-linked carbohydrate structures and extension of O-linked oligosaccharide chains take place, cumulating in the appearance of the mature gpl50. The final processing step involves the cleavage of gpl50 into gp52 and gpl05. By blocking the transport of the glycoprotein precursor to the trans-Golgi compartments with the ionophore monensin, the cleavage process is inhibited, suggesting that the trans-Golgi compartment is the site where gpl50 is cleaved. However, the cleavage process is incomplete, resulting in the formation of multiple disulfide-linked complexes made up of different combinations of gp52, gpl05, and gp150. Therefore, the processing of the major envelope glycoprotein complexes of murine cytomegalovirus resembles that of the gcl/gp55–116 complex of human cytomegalovirus.