Dengue NS2A Protein Orchestrates Virus Assembly.

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.

• Authors: 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
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 26 Issue 5 Pg. 606-622.e8 (11 13 2019) ISSN: 1934-6069 [Electronic] United States
• PMID: 31631053 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• NS2A protein, Dengue virus type 2
• NS3 protein, flavivirus
• RNA, Viral
• Viral Envelope Proteins
• Viral Nonstructural Proteins
• Viral Proteins
• prM protein, Dengue virus type 3
• E protein TH Sman, Dengue virus
• Serine Endopeptidases
• RNA Helicases

Topics

• Aedes
• Animals
• Cell Line
• Chlorocebus aethiops
• Cricetinae
• Dengue Virus (genetics, growth & development)
• HEK293 Cells
• Humans
• Nucleocapsid (biosynthesis)
• RNA Helicases (metabolism)
• RNA, Viral (genetics, metabolism)
• Serine Endopeptidases (metabolism)
• Vero Cells
• Viral Envelope Proteins (metabolism)
• Viral Nonstructural Proteins (genetics, metabolism)
• Viral Proteins (metabolism)
• Virus Assembly (genetics, physiology)