Dengue NS2A Protein Orchestrates Virus Assembly

Xuping Xie, Jing Zou, Xianwen Zhang, Yiyang Zhou, Andrew L. Routh, Congbao Kang, Vsevolod L. Popov, Xinwen Chen, Qing Yin Wang, Hongping Dong, Pei Yong Shi

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Dengue virus assembly requires cleavage of viral C-prM-E polyprotein into three structural proteins (capsid, premembrane, and envelope), packaging of viral RNA with C protein into nucleocapsid, and budding of prM and E proteins into virions. The molecular mechanisms underlying these assembly events are unclear. Here, we show that dengue nonstructural protein 2A (NS2A protein) recruits viral RNA, structural proteins, and protease to the site of virion assembly and coordinates nucleocapsid and virus formation. The last 285 nucleotides of viral 3′ UTR serve as a “recruiting signal for packaging” that binds to a cytosolic loop of NS2A. This interaction allows NS2A to recruit nascent RNA from the replication complex to the virion assembly site. NS2A also recruits the C-prM-E polyprotein and NS2B-NS3 protease to the virion assembly site by interacting with prM, E, and NS3, leading to coordinated C-prM-E cleavage. Mature C protein assembles onto genomic RNA to form nucleocapsid, followed by prM and E envelopment and virion formation.

Original languageEnglish (US)
Pages (from-to)606-622.e8
JournalCell Host and Microbe
Volume26
Issue number5
DOIs
StatePublished - Nov 13 2019

Keywords

  • 3’UTR
  • assembly
  • dengue virus
  • flavivirus
  • nonstructural protein 2A
  • RNA binding

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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