DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV

Danyang Gong; Xinghong Dai; Jonathan Jih; Yun-Tao Liu; Guo-Qiang Bi; Ren Sun; Z Hong Zhou

doi:10.1016/j.cell.2019.07.035

DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV

Cell. 2019 Sep 5;178(6):1329-1343.e12. doi: 10.1016/j.cell.2019.07.035. Epub 2019 Aug 22.

Authors

Danyang Gong¹, Xinghong Dai², Jonathan Jih³, Yun-Tao Liu⁴, Guo-Qiang Bi⁵, Ren Sun⁶, Z Hong Zhou⁷

Affiliations

¹ Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA; 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 230026, China.
⁵ 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 230026, China.
⁶ Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rsun@mednet.ucla.edu.
⁷ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: hong.zhou@ucla.edu.

Abstract

Assembly of Kaposi's sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes (CATCs) and facilitates translocation of an ∼150-kb dsDNA genome, followed by acquisition of a pleomorphic tegument and envelope. Because of deviation from icosahedral symmetry, KSHV portal and tegument structures have largely been obscured in previous studies. Using symmetry-relaxed cryo-EM, we determined the in situ structure of the KSHV portal and its interactions with surrounding capsid proteins, CATCs, and the terminal end of KSHV's dsDNA genome. Our atomic models of the portal and capsid/CATC, together with visualization of CATCs' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Structure-based mutageneses confirm that a triplex deep binding groove for CATCs is a hotspot that holds promise for antiviral development.

Keywords: Kaposi's sarcoma-associated herpesvirus; capsid; cryo-EM; gammaherpesvirus; genome; herpesvirus; microscopy; portal; tegument; virology.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Capsid / metabolism*
Capsid Proteins / chemistry*
Cryoelectron Microscopy / methods
DNA Packaging*
DNA, Viral / metabolism
Genome, Viral
Herpesvirus 8, Human / chemistry*
Herpesvirus 8, Human / physiology*
Humans
Models, Molecular
Sarcoma, Kaposi / virology*
Virus Assembly*

Substances

Capsid Proteins
DNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding