Zuhair, M. et al. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev. Med. Virol. 29, e2034 (2019).
Lantos, P. M. et al. Neighborhood disadvantage is associated with high cytomegalovirus seroprevalence in pregnancy. J. Racial Ethn. Health Dispar. 5, 782–786 (2018).
Plotkin, S. A. & Boppana, S. B. Vaccination against the human cytomegalovirus. Vaccine 37, 7437–7442 (2019).
Chandramouli, S. et al. Structural basis for potent antibody-mediated neutralization of human cytomegalovirus. Sci. Immunol. 2, eaan1457 (2017).
Ciferri, C. et al. Structural and biochemical studies of HCMV gH/gL/gO and pentamer reveal mutually exclusive cell entry complexes. Proc. Natl Acad. Sci. USA 112, 1767–1772 (2015).
Wang, D. & Shenk, T. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc. Natl Acad. Sci. USA 102, 18153–18158 (2005).
Kabanova, A. et al. Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. Nat. Microbiol. 1, 16082 (2016).
Martinez-Martin, N. et al. An unbiased screen for human cytomegalovirus identifies neuropilin-2 as a central viral receptor. Cell 174, 1158–1171 (2018).
Liu, J., Jardetzky, T. S., Chin, A. L., Johnson, D. C. & Vanarsdall, A. L. The human cytomegalovirus trimer and pentamer promote sequential steps in entry into epithelial and endothelial cells at cell surfaces and endosomes. J. Virol. 92, e01336-18 (2018).
Jiang, X. J. et al. UL74 of human cytomegalovirus contributes to virus release by promoting secondary envelopment of virions. J. Virol. 82, 2802–2812 (2008).
Nguyen, C. C. & Kamil, J. P. Pathogen at the gates: human cytomegalovirus entry and cell tropism. Viruses 10, 704 (2018).
Wille, P. T., Knoche, A. J., Nelson, J. A., Jarvis, M. A. & Johnson, D. C. A human cytomegalovirus gO-null mutant fails to incorporate gH/gL into the virion envelope and is unable to enter fibroblasts and epithelial and endothelial cells. J. Virol. 84, 2585–2596 (2010).
Ryckman, B. J., Jarvis, M. A., Drummond, D. D., Nelson, J. A. & Johnson, D. C. Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J. Virol. 80, 710–722 (2006).
Cimato, G., Zhou, X., Brune, W. & Frascaroli, G. Human cytomegalovirus glycoprotein variants governing viral tropism and syncytium formation in epithelial cells and macrophages. J. Virol. 98, e0029324 (2024).
Jarvis, M. A. & Nelson, J. A. Human cytomegalovirus persistence and latency in endothelial cells and macrophages. Curr. Opin. Microbiol. 5, 403–407 (2002).
Caló, S. et al. The human cytomegalovirus UL116 gene encodes an envelope glycoprotein forming a complex with gH independently from gL. J. Virol. 90, 4926–4938 (2016).
Siddiquey, M. N. A. et al. The human cytomegalovirus protein UL116 interacts with the viral endoplasmic-reticulum-resident glycoprotein UL148 and promotes the incorporation of gH/gL complexes into virions. J. Virol. 95, e0220720 (2021).
Vezzani, G. et al. The human cytomegalovirus UL116 glycoprotein is a chaperone to control gH-based complexes levels on virions. Front. Microbiol. 12, 630121 (2021).
Nobre, L. V. et al. Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions. eLife 8, e49894 (2019).
Nemčovičová, I., Benedict, C. A. & Zajonc, D. M. Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non-canonical death receptor interactions. PLoS Pathog. 9, e1003224 (2013).
Tomasec, P. et al. Downregulation of natural killer cell-activating ligand CD155 by human cytomegalovirus UL141. Nat. Immunol. 6, 181–188 (2005).
Hsu, J.-L. et al. Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141. PLoS Pathog. 11, e1004811 (2015).
Vlahava, V.-M. et al. Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus. J. Clin. Invest. 131, e139296 (2021).
Sinzger, C. et al. Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E. J. Gen. Virol. 89, 359–368 (2008).
Koehler, M., Delguste, M., Sieben, C., Gillet, L. & Alsteens, D. Initial step of virus entry: virion binding to cell-surface glycans. Annu. Rev. Virol. https://doi.org/10.1146/annurev-virology-122019-070025 (2020).
Li, Y. et al. The importance of glycans of viral and host proteins in enveloped virus infection. Front. Immunol. 12, 638573 (2021).
Feng, T. et al. Glycosylation of viral proteins: implication in virus–host interaction and virulence. Virulence 13, 670–683 (2022).
Nemčovičová, I. & Zajonc, D. M. The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding. Acta Crystallogr. D 70, 851–862 (2014).
Kschonsak, M. et al. Structural basis for HCMV pentamer receptor recognition and antibody neutralization. Sci. Adv. 8, eabm2536 (2022).
Kschonsak, M. et al. Structures of HCMV trimer reveal the basis for receptor recognition and cell entry. Cell 184, 1232–1244 (2021).
Scrivano, L., Sinzger, C., Nitschko, H., Koszinowski, U. H. & Adler, B. HCMV spread and cell tropism are determined by distinct virus populations. PLoS Pathog. 7, e1001256 (2011).
Permar, S. R., Schleiss, M. R. & Plotkin, S. A. A vaccine against cytomegalovirus: how close are we? J. Clin. Invest. 135, e182317 (2025).
Cha, T. A. et al. Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J. Virol. 70, 78–83 (1996).
Wasilewski, S., Calder, L. J., Grant, T. & Rosenthal, P. B. Distribution of surface glycoproteins on influenza A virus determined by electron cryotomography. Vaccine 30, 7368–7373 (2012).
Conley, M. J. et al. Helical ordering of envelope-associated proteins and glycoproteins in respiratory syncytial virus. EMBO J. 41, e109728 (2022).
Xu, K. et al. Crystal structure of the pre-fusion Nipah virus fusion glycoprotein reveals a novel hexamer-of-trimers assembly. PLoS Pathog. 11, e1005322 (2015).
Beilstein, F. et al. Dynamic organization of Herpesvirus glycoproteins on the viral envelope revealed by super-resolution microscopy. PLoS Pathog. 15, e1008209 (2019).
Casalino, L. et al. Beyond shielding: the roles of glycans in SARS-CoV-2 spike protein. ACS Cent. Sci. https://doi.org/10.1021/acscentsci.0c01056 (2020).
Watanabe, Y. et al. Structure of the Lassa virus glycan shield provides a model for immunological resistance. Proc. Natl Acad. Sci. USA 115, 7320–7325 (2018).
Peng, W. et al. Glycan shield of the ebolavirus envelope glycoprotein GP. Commun. Biol. 5, 785 (2022).
Stewart-Jones, G. B. E. et al. Trimeric HIV-1-Env structures define glycan shields from clades A, B, and G. Cell 165, 813–826 (2016).
Watanabe, Y., Bowden, T. A., Wilson, I. A. & Crispin, M. Exploitation of glycosylation in enveloped virus pathobiology. Biochim. Biophys. Acta Gen. Subj. 1863, 1480–1497 (2019).
Kaye, J. F., Gompels, U. A. & Minson, A. C. Glycoprotein H of human cytomegalovirus (HCMV) forms a stable complex with the HCMV UL115 gene product. J. Gen. Virol. 73, 2693–2698 (1992).
Hahn, A. S. et al. A recombinant rhesus monkey rhadinovirus deleted of glycoprotein L establishes persistent infection of rhesus macaques and elicits conventional T cell responses. J. Virol. 94, e01093-19 (2020).
Smith, W. et al. Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses. Cell Host Microbe 13, 324–335 (2013).
Zhou, M., Lanchy, J.-M. & Ryckman, B. J. Human cytomegalovirus gH/gL/gO promotes the fusion step of entry into all cell types, whereas gH/gL/UL128-131 broadens virus tropism through a distinct mechanism. J. Virol. 89, 8999–9009 (2015).
Fornara, C. et al. Fibroblast, epithelial and endothelial cell-derived human cytomegalovirus strains display distinct neutralizing antibody responses and varying levels of gH/gL complexes. Int. J. Mol. Sci. 24, 4417 (2023).
Nguyen, C. C., Siddiquey, M. N. A., Zhang, H., Li, G. & Kamil, J. P. Human cytomegalovirus tropism modulator UL148 interacts with SEL1L, a cellular factor that governs endoplasmic reticulum-associated degradation of the viral envelope glycoprotein gO. J. Virol. 92, e00688–18 (2018).
Wang, D. et al. The ULb′ region of the human cytomegalovirus genome confers an increased requirement for the viral protein kinase UL97. J. Virol. 87, 6359–6376 (2013).
Caposio, P. et al. Characterization of a live-attenuated HCMV-based vaccine platform. Sci. Rep. 9, 19236 (2019).
Hobom, U., Brune, W., Messerle, M., Hahn, G. & Koszinowski, U. H. Fast screening procedures for random transposon libraries of cloned herpesvirus genomes: mutational analysis of human cytomegalovirus envelope glycoprotein genes. J. Virol. 74, 7720–7729 (2000).
Tischer, B. K., Smith, G. A. & Osterrieder, N. En passant mutagenesis: a two step markerless red recombination system. Methods Mol. Biol. 634, 421–430 (2010).
Tischer, B. K., von Einem, J., Kaufer, B. & Osterrieder, N. Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli. Biotechniques 40, 191–197 (2006).
Bossen, C. et al. Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human. J. Biol. Chem. 281, 13964–13971 (2006).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Bepler, T. et al. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat. Methods 16, 1153–1160 (2019).
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Sanchez-Garcia, R. et al. DeepEMhancer: a deep learning solution for cryo-EM volume post-processing. Commun. Biol. 4, 874 (2021).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Croll, T. I. ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps. Acta Crystallogr. D 74, 519–530 (2018).
Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D 75, 861–877 (2019).
Evans, R. et al. Protein complex prediction with AlphaFold-Multimer. Preprint at bioRxiv https://doi.org/10.1101/2021.10.04.463034 (2021).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Mirdita, M. et al. ColabFold: making protein folding accessible to all. Nat. Methods 19, 679–682 (2022).
Baker, N. A., Sept, D., Joseph, S., Holst, M. J. & McCammon, J. A. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl Acad. Sci. USA 98, 10037–10041 (2001).
Dolinsky, T. J. et al. PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res. 35, W522–W525 (2007).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
Zhang, H. et al. The human cytomegalovirus nonstructural glycoprotein UL148 reorganizes the endoplasmic reticulum. mBio 10, e02110–e02119 (2019).