Atomic structure of the human herpesvirus 6B capsid and capsid-associated tegument complexes

Human herpesvirus 6B (HHV-6B) belongs to the β-herpesvirus subfamily of the Herpesviridae. To understand capsid assembly and capsid-tegument interactions, here we report atomic structures of HHV-6B capsid and capsid-associated tegument complex (CATC) obtained by cryoEM and sub-particle reconstruction. Compared to other β-herpesviruses, HHV-6B exhibits high similarity in capsid structure but organizational differences in its CATC (pU11 tetramer). 180 “VΛ”-shaped CATCs are observed in HHV-6B, distinguishing from the 255 “Λ”-shaped dimeric CATCs observed in murine cytomegalovirus and the 310 “Δ”-shaped CATCs in human cytomegalovirus. This trend in CATC quantity correlates with the increasing genomes sizes of these β-herpesviruses. Incompatible distances revealed by the atomic structures rationalize the lack of CATC’s binding to triplexes Ta, Tc, and Tf in HHV-6B. Our results offer insights into HHV-6B capsid assembly and the roles of its tegument proteins, including not only the β-herpesvirus-specific pU11 and pU14, but also those conserved across all subfamilies of Herpesviridae.


Statistics
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Data analysis
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An open source software MotionCor2 was used to align and average each HHV-6B movies; An open source software CTFFIND4 was used to determine the defocus of each micrograph; An open source softwere Relion was used to perform 2D classification, 3D refinement, and 3D reconstruction for either bin4 HHV-6B viron/NIEP particles or bin1 2f/3f/5f sub-particles; An open source code Scipion was used to determine the location and recalculate the defocus of each 2f/3f/5f sub-particle; An open source web server SWISS-MODEL was used to build the homology models within one HHV-6B asymmetric unit; An open source software Phenix was used to build the HHV-6B atomic models; An open source softwere Chimera was used to realize model visualization; An open source web server wwPDB validation was used to describe the geometric outliers and report the quality of the atomic models; An open source software Coot was uesd to fix the atomic models manually.