Genetic and biochemical characterizations of Zika virus NS2A protein

Xianwen Zhang, Xuping Xie, Jing Zou, Hongjie Xia, Chao Shan, Xinwen Chen, Pei-Yong Shi

Research output: Contribution to journalArticle

Abstract

Zika virus (ZIKV) can cause devastating congenital Zika syndromes in pregnant women and Guillain-Barre syndrome in adults. Understanding the molecular mechanism of ZIKV replication is essential for antiviral and vaccine development. Here we report the structural and functional characterization of ZIKV NS2A protein. Biochemical structural probing suggests that ZIKV NS2A has a single segment that traverses the ER membrane and six segments that peripherally associate with the ER membrane. Functional analysis has defined distinct NS2A residues essential for viral RNA synthesis or virion assembly. Only the virion assembly-defective mutants, but not the RNA synthesis-defective mutants, could be rescued through trans complementation with a wide-type NS2A protein. These results suggest that the NS2A molecules in virion assembly complex could be recruited in trans, whereas the NS2A molecules in viral replication complex must be recruited in cis. Together with previous results, we propose a flavivirus assembly model where NS2A plays a central role in modulating viral structural and nonstructural proteins as well as genomic RNA during virion assembly.

Original languageEnglish (US)
Pages (from-to)585-602
Number of pages18
JournalEmerging Microbes and Infections
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Virion
Molecular Biology
Proteins
Viral Nonstructural Proteins
RNA
Viral Structural Proteins
Flavivirus
Guillain-Barre Syndrome
Membranes
Viral RNA
Virus Replication
Antiviral Agents
Pregnant Women
Vaccines
Zika Virus

Keywords

  • flavivirus NS2A
  • flavivirus replication
  • membrane topology
  • virion assembly
  • Zika virus

ASJC Scopus subject areas

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology

Cite this

Genetic and biochemical characterizations of Zika virus NS2A protein. / Zhang, Xianwen; Xie, Xuping; Zou, Jing; Xia, Hongjie; Shan, Chao; Chen, Xinwen; Shi, Pei-Yong.

In: Emerging Microbes and Infections, Vol. 8, No. 1, 01.01.2019, p. 585-602.

Research output: Contribution to journalArticle

Zhang, Xianwen ; Xie, Xuping ; Zou, Jing ; Xia, Hongjie ; Shan, Chao ; Chen, Xinwen ; Shi, Pei-Yong. / Genetic and biochemical characterizations of Zika virus NS2A protein. In: Emerging Microbes and Infections. 2019 ; Vol. 8, No. 1. pp. 585-602.
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