Structural highlights
Publication Abstract from PubMedHuman cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the incomplete understanding of the diverse protein complexes the virus uses to infect cells. In Herpesviridae, the gH/gL glycoprotein heterodimer is expected to be a basal element of virion cell entry machinery. For HCMV, gH/gL forms a "trimer" with gO and a "pentamer" with UL128, UL130, and UL131A, with each complex binding distinct receptors to enter varied cell types. Here, we reveal a third glycoprotein complex, abundant in HCMV virions, which significantly enhances infection of endothelial cells. In this "3-mer" complex, gH, without gL, associates with UL116 and UL141, an immunoevasin previously known to function in an intracellular role. Cryo-EM reveals the virion-surface 3-mer is structurally unique among Herpesviridae gH complexes, with gH-only scaffolding, UL141-mediated dimerization and a heavily glycosylated UL116 cap. Given that antibodies directed at gH and UL141 each can restrict HCMV replication, our work highlights this virion surface complex as a new target for vaccines and antiviral therapies. A noncanonical glycoprotein H complex enhances cytomegalovirus entry.,Norris MJ, Henderson LA, Siddiquey MNA, Yin J, Yoo K, Brunel S, Saphire EO, Benedict CA, Kamil JP bioRxiv [Preprint]. 2024 Oct 13:2024.10.13.617647. doi: , 10.1101/2024.10.13.617647. PMID:39416215[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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