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Journal of Virology, October 2000, p. 9646-9654, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Three-Dimensional Structure of the Human Herpesvirus 8 Capsid

Lijun Wu,1 Pierrette Lo,2 Xuekui Yu,2 James K. Stoops,2 B. Forghani,1 and Z. Hong Zhou2,*

Viral and Rickettsial Disease Laboratory, Division of Communicable Disease Control, California Department of Health Services, Berkeley, California 94720,1 and Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 770302

Received 31 May 2000/Accepted 13 July 2000

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 and 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-acetate to obtain HHV-8 capsids for electron cryomicroscopy and computer reconstruction. The 3D structure of the HHV-8 capsids revealed a capsid shell composed of 12 pentons, 150 hexons, and 320 triplexes arranged on a T=16 icosahedral lattice. This structure is similar to those of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), which are prototypical members of alpha- and betaherpesviruses, respectively. The inner radius of the HHV-8 capsid is identical to that of the HSV-1 capsid but is smaller than that of the HCMV capsid, which is consistent with the relative sizes of the genomes they enclose. While the HHV-8 capsid exhibits many structural similarities to the HSV-1 capsid, our reconstruction shows two major differences: its hexons lack the "horn-shaped" VP26 densities bound to the HSV-1 hexon subunits, and the HHV-8 triplexes appear smaller and less elongated than those of HSV-1. These differences are in excellent agreement with our sequence comparisons of HHV-8 and HSV-1 capsid proteins. This gammaherpesvirus capsid structure complements previous structural studies on alpha- and betaherpesviruses in providing an account of structural similarities and differences among capsids representing all human herpesvirus subfamilies.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, TX 77030. Phone: (713) 500-5358. Fax: (713) 500-0730. E-mail: Z.H.Zhou{at}uth.tmc.edu.

Journal of Virology, October 2000, p. 9646-9654, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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