Structural basis for genome packaging, retention, and ejection in human cytomegalovirus

Zhihai Li, Jingjing Pang, Lili Dong and Xuekui Yu ()
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Zhihai Li: Chinese Academy of Sciences
Jingjing Pang: Chinese Academy of Sciences
Lili Dong: Chinese Academy of Sciences
Xuekui Yu: Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract How the human cytomegalovirus (HCMV) genome—the largest among human herpesviruses—is packaged, retained, and ejected remains unclear. We present the in situ structures of the symmetry-mismatched portal and the capsid vertex-specific components (CVSCs) of HCMV. The 5-fold symmetric 10-helix anchor—uncommon among known portals—contacts the portal-encircling DNA, which is presumed to squeeze the portal as the genome packaging proceeds. We surmise that the 10-helix anchor dampens this action to delay the portal reaching a “head-full” packaging state, thus facilitating the large genome to be packaged. The 6-fold symmetric turret, latched via a coiled coil to a helix from a major capsid protein, supports the portal to retain the packaged genome. CVSCs at the penton vertices—presumed to increase inner capsid pressure—display a low stoichiometry, which would aid genome retention. We also demonstrate that the portal and capsid undergo conformational changes to facilitate genome ejection after viral cell entry.

Date: 2021
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DOI: 10.1038/s41467-021-24820-3

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