Three-dimensional structure of the human herpesvirus 8 capsid

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus implicated in all forms of Kaposi's sarcoma and certain lymphomas. HHV-8 has been extensively characterized, both biochemically an d immunologically, since its first description in 1994. However, its three- dimensional (3D) structure remained heretofore undetermined largely due to difficulties in viral purification. We have used log-phase cultures of body cavity-based lymphoma 1 cells induced with 12-O-tetradecanoylphorbol-13-ac etate to obtain HHV-8 capsids for electron cryomicroscopy and computer reco nstruction. The 3D structure of the HHV-8 capsids revealed a capsid shell c omposed of 12 pentons, 150 herons, and 320 triplexes arranged on a T=16 ico sahedral lattice. This structure is similar to those of herpes simplex viru s type 1 (HSV-1) and human cytomegalovirus (HCMV), which are prototypical m embers of alpha- and betaherpesviruses, respectively. The inner radius of t he HHV-8 capsid is identical to that of the HSV-1 capsid but is smaller tha n that of the HCMV capsid, which is consistent with the relative sizes of t he genomes they enclose. While the HHV-8 capsid exhibits many structural si milarities to the HSV-1 capsid, our reconstruction shows two major differen ces: its herons lack the "horn-shaped" VP26 densities bound to the HSV-1 he xon subunits, and the HHV-8 triplexes appear smaller and less elongated tha n those of HSV-1, These differences are in excellent agreement with our seq uence comparisons of HHV-8 and HSV-1 capsid proteins. This gammaherpesvirus capsid structure complements previous structural studies on alpha- and bet aherpesviruses in providing an account of structural similarities and diffe rences among capsids representing all human herpesvirus subfamilies.