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

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Abstract

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.

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Acknowledgments

This work was supported by grants from the Foundation Recherche Médicale (“Equipe FRM”, RJ), the Association pour la Recherche sur le Cancer (ARC, no 5051), the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Centre National de la Recherche Scientifique (CNRS). KT was supported by a research fellowship of the Université Paris Descartes (France). The excellent technical assistance of Ramona Ansorge, Manuela Michel, and Norbert Zanker is kindly acknowledged.

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Authors and Affiliations

  1. Institut für Virologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Svenja Wagner, Franziska Arnold, Zeguang Wu, Axel Schubert, Thomas Mertens & Detlef Michel

  2. Institut für Molekulare Virologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Franziska Arnold

  3. Institut für Pharmakologie und Toxikologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Claudia Walliser

  4. Inserm U1016, CNRS 8104, Institut Cochin, Université Paris Descartes, 22 rue Méchain, 75014, Paris, France

    Kenjiro Tadagaki & Ralf Jockers

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  1. Svenja Wagner
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Wagner, S., Arnold, F., Wu, Z. et al. The 7-transmembrane protein homologue UL78 of the human cytomegalovirus forms oligomers and traffics between the plasma membrane and different intracellular compartments. Arch Virol 157, 935–949 (2012). https://doi.org/10.1007/s00705-012-1246-6

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