Structurally similar woodchuck and human hepadnavirus core proteins have distinctly different temperature dependences of assembly

Alexander A. Kukreja, Joseph C.Y. Wang, Elizabeth Pierson, David Z. Keifer, Lisa Selzer, Zhenning Tan, Bogdan Dragnea, Martin F. Jarrold, Adam Zlotnick

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Woodchuck hepatitis virus (WHV), a close relative of human hepatitis B virus (HBV), has been a key model for disease progression and clinical studies. Sequences of the assembly domain ofWHVand HBV core proteins (wCp149 and hCp149, respectively) have 65% identity, suggesting similar assembly behaviors. We report a cryo-electron microscopy (cryo-EM) structure of the WHVcapsid at nanometer resolution and characterization of wCp149 assembly. At this resolution, the T=4 capsid structures of WHVand HBV are practically identical. In contrast to their structural similarity, wCp149 demonstrates enhanced assembly kinetics and stronger dimer-dimer interactions than hCp149: at 23°C and at 100mMionic strength, the pseudocritical concentrations of assembly of wCp149 and hCp149 are 1.8 μM and 43.3 μM, respectively. Transmission electron microscopy reveals that wCp149 assembles into predominantly T=4 capsids with a sizeable population of larger, nonicosahedral structures. Charge detection mass spectrometry indicates that T=3 particles are extremely rare compared to the ~5% observed in hCp149 reactions. Unlike hCp149, wCp149 capsid assembly is favorable over a temperature range of 4°C to 37°C; van't Hoff analyses relate the differences in temperature dependence to the high positive values for heat capacity, enthalpy, and entropy of wCp149 assembly. Because the final capsids are so similar, these findings suggest that free wCp149 and hCp149 undergo different structural transitions leading to assembly. The difference in the temperature dependence of wCp149 assembly may be related to the temperature range of its hibernating host.

Original languageEnglish (US)
Pages (from-to)14105-14115
Number of pages11
JournalJournal of virology
Volume88
Issue number24
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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