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

• DOI: 10.1038/s41467-019-13064-x
• Publication Date: 2019-11-25T11:02:49Z
• Authors: Yibo Zhang; Wei Liu; Zihang Li; Vinay Kumar; Ana L. Alvarez-Ca...; Emily C. Leibovitch; Yanxiang Cui; Ye Mei; Guo-Qiang Bi; Steve Jacobson; Z. Hong Zhou
• Keywords: 0301 basic medicine; Science; Herpesvirus 6, Human; Roseolovirus Infections; Genome, Viral; Article; Inorganic Chemistry; Viral Matrix Proteins; 03 medical and health sciences; Capsid; Humans; Herpesvirus 6; Viral; 0303 health sciences; Genome; Q; Cryoelectron Microscopy; 500; 540; 3. Good health; Emerging Infectious Diseases; Infectious Diseases; Multiprotein Complexes; Chemical Sciences; Sexually Transmitted Infections; Capsid Proteins; Human; Protein Binding

AbstractHuman 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.