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Abstract
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.
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1 Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China (USTC), Hefei, Anhui, China; California NanoSystems Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
2 Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China (USTC), Hefei, Anhui, China; California NanoSystems Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA; State Key Laboratory of Precision Spectroscopy, School of Physics and Electronic Science, East China Normal University (ECNU), Shanghai, China
3 California NanoSystems Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA
4 Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, MD, USA
5 California NanoSystems Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
6 State Key Laboratory of Precision Spectroscopy, School of Physics and Electronic Science, East China Normal University (ECNU), Shanghai, China
7 Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China (USTC), Hefei, Anhui, China