The structural basis of herpesvirus entry

Sarah A. Connolly*, Theodore S. Jardetzky, Richard Longnecker*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

145 Scopus citations


Herpesviruses are ubiquitous, double-stranded DNA, enveloped viruses that establish lifelong infections and cause a range of diseases. Entry into host cells requires binding of the virus to specific receptors, followed by the coordinated action of multiple viral entry glycoproteins to trigger membrane fusion. Although the core fusion machinery is conserved for all herpesviruses, each species uses distinct receptors and receptor-binding glycoproteins. Structural studies of the prototypical herpesviruses herpes simplex virus 1 (HSV-1), HSV-2, human cytomegalovirus (HCMV) and Epstein–Barr virus (EBV) entry glycoproteins have defined the interaction sites for glycoprotein complexes and receptors, and have revealed conformational changes that occur on receptor binding. Recent crystallography and electron microscopy studies have refined our model of herpesvirus entry into cells, clarifying both the conserved features and the unique features. In this Review, we discuss recent insights into herpesvirus entry by analysing the structures of entry glycoproteins, including the diverse receptor-binding glycoproteins (HSV-1 glycoprotein D (gD), EBV glycoprotein 42 (gp42) and HCMV gH–gL–gO trimer and gH–gL–UL128–UL130–UL131A pentamer), as well gH–gL and the fusion protein gB, which are conserved in all herpesviruses.

Original languageEnglish (US)
Pages (from-to)110-121
Number of pages12
JournalNature Reviews Microbiology
Issue number2
StatePublished - Feb 2021

ASJC Scopus subject areas

  • Infectious Diseases
  • General Immunology and Microbiology
  • Microbiology


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