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Cited by 14Cytomegalovirus and herpesvirus researchHerpesvirus Infections and TreatmentsViral-associated cancers and disorders

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The GATE glycoprotein complex enhances human cytomegalovirus entry in endothelial cells

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Norris, Michael J., Henderson, Lauren A., Siddiquey, Mohammed N. A., Yin, Jieyun, Yoo, Kwangsun, Brunel, Simon, Mor, Michael, Saphire, Erica Ollmann, Benedict, Chris A., Kamil, Jeremy P.·2025·Nature Microbiology
DOI 10.1038/s41564-025-02025-4PMC PMC12312674

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Abstract

Human cytomegalovirus can cause severe birth defects upon infection in pregnant women and complications in immunocompromised patients. A major challenge for vaccine design is our incomplete understanding of the diverse protein complexes this virus uses to infect cells. In Herpesviridae, glycoproteins H and L (gH and gL) form complexes with other viral proteins that bind receptors to mediate cell-type-specific entry. Here we identify a distinct gH complex that is abundant on human cytomegalovirus virions and enhances infection of endothelial cells. In this complex, gH associates with UL116 and UL141 (an immunoevasin previously known to function intracellularly) but not with gL. We term this the gH-associated tropism and entry (GATE) complex and provide the cryo-electron microscopy structure at ~3.5 Å. The structure shows gH-only scaffolding, UL141-mediated dimerization and a heavily glycosylated UL116 cap. These findings identify a third virion surface complex that promotes cell entry and may represent a new target for vaccines or antiviral therapies.

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Metadata

Authors
Norris, M. J., Henderson, L. A., Siddiquey, M. N. A., Yin, J., Yoo, K., Brunel, S., Mor, M., Saphire, E. O., Benedict, C. A., & Kamil, J. P.
Affiliations
  • La Jolla Institute for Immunology (US)
  • Louisiana State University (US)
Corresponding author
  • Saphire, Erica Ollmann
  • Benedict, Chris A.
  • Kamil, Jeremy P.
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2025-06-30
Volume
10
Issue
7
Pages
1605-1616
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-025-02025-4
PMC
PMC12312674
OpenAlex
W4411829974
Cited by
14
References
1
Citations by year
2026: 7 · 2025: 7
FWCI
9.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • U.S. Department of Health and Human Services (R01AI101423, U19109762-S1, T32HL155022, P20-GM134974, R01AI139749, R01AI116851)
  • GHR Foundation
  • National Institutes of Health (AI139749, AI101423)
  • National Heart, Lung, and Blood Institute (T32HL155022)
  • National Institute of General Medical Sciences (P20GM134974)
  • National Institute of Allergy and Infectious Diseases (R01AI101423, R01AI139749, U19AI109762, R56AI101423, R01AI116851)
Topics
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
  • Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords
human cytomegalovirus, viral entry, endothelial cells, viral tropism, cryo-EM structure, vaccine targets, antiviral therapy

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