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Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids.

Wang W, Zheng Q, Pan D, Yu H, Fu W, Liu J, He M, Zhu R, Cai Y, Huang Y, Zha Z, Chen Z, Ye X, Han J, Que Y, Wu T, Zhang J, Li S, Zhu H, Zhou ZH, Cheng T, Xia N
Nat Microbiol 5 1542-1552 (2020)
Cited: 5 times
EuropePMC logo PMID: 32895526

Abstract

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP-the largest among human herpesviruses-uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.

Articles - 6lgl mentioned but not cited (1)

  1. Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids. Wang W, Zheng Q, Pan D, Yu H, Fu W, Liu J, He M, Zhu R, Cai Y, Huang Y, Zha Z, Chen Z, Ye X, Han J, Que Y, Wu T, Zhang J, Li S, Zhu H, Zhou ZH, Cheng T, Xia N. Nat Microbiol 5 1542-1552 (2020)


Reviews citing this publication (1)

  1. The Ins and Outs of Herpesviral Capsids: Divergent Structures and Assembly Mechanisms across the Three Subfamilies. Draganova EB, Valentin J, Heldwein EE. Viruses 13 1913 (2021)

Articles citing this publication (3)

  1. Structure of human cytomegalovirus virion reveals host tRNA binding to capsid-associated tegument protein pp150. Liu YT, Strugatsky D, Liu W, Zhou ZH. Nat Commun 12 5513 (2021)
  2. Structures of pseudorabies virus capsids. Wang G, Zha Z, Huang P, Sun H, Huang Y, He M, Chen T, Lin L, Chen Z, Kong Z, Que Y, Li T, Gu Y, Yu H, Zhang J, Zheng Q, Chen Y, Li S, Xia N. Nat Commun 13 1533 (2022)
  3. A novel recombinant ORF7-siRNA delivered by flexible nano-liposomes inhibits varicella zoster virus infection. Pei J, Tian Y, Ye W, Han J, Dang Y, Cheng T, Wang W, Zhao Y, Ye W, Huangfu S, Li Y, Zhang F, Lei Y, Qian A. Cell Biosci 13 167 (2023)


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