Cryo-EM structure of a herpesvirus capsid at 3.1 Å

• Published in: Science (American Association for the Advancement of Science) Vol. 360; no. 6384
• Main Authors: Yuan, Shuai, Wang, Jialing, Zhu, Dongjie, Wang, Nan, Gao, Qiang, Chen, Wenyuan, Tang, Hao, Wang, Junzhi, Zhang, Xinzheng, Liu, Hongrong, Rao, Zihe, Wang, Xiangxi
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 06.04.2018
• Subjects: Activation; Adaptation; Assembly; Atomic structure; Capsid protein; Capsids; Chemical bonds; Chemical compounds; Complexity; Cytomegalovirus; Deoxyribonucleic acid; Disulfide bonds; DNA; Drug development; Electron microscopy; Epstein-Barr virus; Genomes; Herpes labialis; Herpes simplex; Herpes viruses; Hexons; HIV; Host range; Human immunodeficiency virus; Icosahedral phase; Image processing; Image reconstruction; Intermediates; Latency; Latent infection; Microenvironments; Microscopy; Nuclei; Nuclei (cytology); Penton protein; Pharmacology; Proteins; Reagents; Recurrent infection; Sarcoma; Sexually transmitted diseases; STD; Structure-function relationships; Tegument; Transmission electron microscopy; Triangulation; Tumors; Virions; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aao7283

The herpesvirus family includes herpes simplex virus type 1 (HSV-1), which causes cold sores, and type 2 (HSV-2), which causes genital herpes. Herpesviruses comprise a large DNA genome enclosed in a large and complex protein cage called a capsid (see the Perspective by Heldwein). Dai and Zhou used electron microscopy to determine a high-resolution structure of the HSV-1 capsid bound to the tegument proteins that occupy the space between the capsid and the nuclear envelope. The structure suggests how these components may play a role in viral transport. Yuan et al. describe a higher-resolution structure of an HSV-2 capsid, providing insight into how the shell assembles and is stabilized. Science , this issue p. eaao7298 , p. eaao7283 ; see also p. 34 Electron microscopy structures provide insight into the function of the herpesviruses that cause cold sores and genital herpes. Structurally and genetically, human herpesviruses are among the largest and most complex of viruses. Using cryo–electron microscopy (cryo-EM) with an optimized image reconstruction strategy, we report the herpes simplex virus type 2 (HSV-2) capsid structure at 3.1 angstroms, which is built up of about 3000 proteins organized into three types of hexons (central, peripentonal, and edge), pentons, and triplexes. Both hexons and pentons contain the major capsid protein, VP5; hexons also contain a small capsid protein, VP26; and triplexes comprise VP23 and VP19C. Acting as core organizers, VP5 proteins form extensive intermolecular networks, involving multiple disulfide bonds (about 1500 in total) and noncovalent interactions, with VP26 proteins and triplexes that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to 46 different conformers that assemble into a massive quasisymmetric shell, exemplifying the structural and functional complexity of HSV.