CryoEM Atomic Structure Of The Human Herpesvirus 6B Capsid And Capsid-Associated Tegument Complexes

Human herpesvirus 6B(HHV-6B),primarily implicated in roseola and neurodegenerative conditions,belongs to the ?-herpesvirus subfamily of the Herpesviridae.A hallmark difference of p-herpesviruses from both a-herpesviruses and?-herpesviruses is the ?-herpesvirus-specific phosphoproteins[pU11 in HHV-6B and pUL32/pp150 in human cytomegalovirus(HCMV)],which,in HCMV,forms capsid-associated tegument complexes(CATCs)with multiple functions including securing its large genome of 235-kilobase pairs.To understand capsid assembly,particularly the organization of pU11,here we report the first atomic structure of HHV-6B obtained by cryoEM and sub-particle reconstruction.HHV-6B exhibits high similarity in capsid structure but striking differences in CATC organization when compared to other ?-herpesviruses.180 MVAM-shaped tetrameric CATCs are observed in HHV-6B,distinguishing from the 255 "?"-shaped dimeric CATCs observed in murine cytomegalovirus(MCMV)and the 310 "?"-shaped CATCs in HCMV.This trend in CATC quantity correlates with the increasing genomes sizes of these ?-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 ?-herpesvirus-specific pU11 and pU 14,but also tegument proteins conserved across all sub-families of Herpesviridae.