The 7-transmembrane protein homologue UL78 of the human cytomegalovirus forms oligomers and traffics between the plasma membrane and different intracellular compartments

• Published in: Archives of virology 2012-05, Vol.157 (5), p.935-949
• Main Authors: Wagner, Svenja, Arnold, Franziska, Wu, Zeguang, Schubert, Axel, Walliser, Claudia, Tadagaki, Kenjiro, Jockers, Ralf, Mertens, Thomas, Michel, Detlef
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cell Line; Cell Membrane - chemistry; Cell Membrane - genetics; Cell Membrane - metabolism; Cytomegalovirus; Cytomegalovirus - chemistry; Cytomegalovirus - genetics; Cytomegalovirus - metabolism; Cytomegalovirus Infections - metabolism; Cytomegalovirus Infections - virology; Cytoplasm - metabolism; Cytoplasm - virology; Dimerization; Endosomes - metabolism; Endosomes - virology; Fundamental and applied biological sciences. Psychology; Herpes viruses; Human cytomegalovirus; Humans; Infectious Diseases; Ligands; Localization; Medical Microbiology; Membranes; Microbiology; Miscellaneous; Mutagenesis; Original Article; Protein Structure, Secondary; Protein Transport; Proteins; trans-Golgi Network - metabolism; trans-Golgi Network - virology; Virology
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-012-1246-6

The human cytomegalovirus (HCMV) UL78 ORF is considered to encode an orphan 7-transmembrane receptor. However, until now, the UL78 protein (pUL78) has not been characterized. Here, we have investigated the expression of pUL78 and found it mainly associated with the endoplasmic reticulum. However, we provide evidence that pUL78 is also localized on the cell surface from where it is quickly endocytosed. Colocalization with adaptin and EEA-1 implies that at least a small amount of pUL78 is transported to the trans Golgi network and early endosomes. Using a bimolecular fluorescence complementation assay and co-immunoprecipitation experiments, we were able to find homomeric and heteromeric structure formations of pUL78 and the US28 protein, respectively. However, the absence of pUL78 had no effect on the accumulation of inositol phosphate triggered by the US28 protein. In summary, our results suggest that the UL78 protein of HCMV traffics between the cell surface and cytoplasm, from where it might be recycled via early endosomes.