Details

Autor(en) / Beteiligte

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

Titel

Dengue NS2A Protein Orchestrates Virus Assembly

Ist Teil von

• Cell host & microbe, 2019-11, Vol.26 (5), p.606-622.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Dengue NS2A recruits C-prM-E structural proteins and a protease to virion assembly site•A cytosolic loop of NS2A recruits the 3′ UTR of viral RNA to virion assembly site•A coordinated C-prM cleavage enables viral RNA encapsidation and virion formation Xie et al. use genetic, biochemical, and imaging approaches to demonstrate that dengue virus NS2A protein recruits viral structural proteins, a protease complex, and genomic RNA to the virion assembly site. The resulting interactions enable a coordinated cleavage of viral C-prM protein to facilitate viral RNA encapsidation and virion formation.