Structural Insights into Alphavirus Assembly Revealed by the Cryo-EM Structure of Getah Virus.

Ming Wang,Decheng Yang,Jiaqi Li,Zhenzhao Sun,Chenxi Cui,Shida Wang,Zaisi Liu,Xiangxi Wang,Bingchen Du,Xijun He,Xinyu Wei,Pengfei Wang,Chunguo Liu,Jingfei Wang,Lili Wei,Weiyao Sun,Xinzheng Zhang,Jing Zhu,Zhibin Shi

doi:10.3390/v14020327

Abstract

Getah virus (GETV) is a member of the alphavirus genus, and it infects a variety of animal species, including horses, pigs, cattle, and foxes. Human infection with this virus has also been reported. The structure of GETV has not yet been determined. In this study, we report the cryo-EM structure of GETV at a resolution of 3.5 Å. This structure reveals conformational polymorphism of the envelope glycoproteins E1 and E2 at icosahedral 3-fold and quasi-3-fold axes, which is believed to be a necessary organization in forming a curvature surface of virions. In our density map, three extra densities are identified, one of which is believed a “pocket factor”; the other two are located by domain D of E2, and they may maintain the stability of E1/E2 heterodimers. We also identify three N-glycosylations at E1 N141, E2 N200, and E2 N262, which might be associated with receptor binding and membrane fusion. The resolving of the structure of GETV provides new insights into the structure and assembly of alphaviruses and lays a basis for studying the differences of biology and pathogenicity between arthritogenic and encephalitic alphaviruses.

Highlights

Getah virus (GETV) is a mosquito-borne RNA virus belonging to the Alphavirus genus in the Togaviridae family, which contains several human pathogens, such as chikungunya virus (CHIKV), Semliki Forest virus (SFV), Venezuelan equine encephalitis virus (VEEV), and Sindbis virus (SINV), etc
The three blocks of the T = 4 icosahedral lattice were as follows: Block 1 as the icosahedral five-fold of type-2 quasi-three-folds (B1), Block 2 as four type-2 quasi-three-folds flanked by two type-1 symmetrical trimers across the icosahedral two-fold axis (B2), and Block 3 was one type-1 symmetrical trimer surrounded by three type-2 quasi-three-folds about the icosahedral three-fold axis (B3) (Figure S1C)
A slice through the 3D density map (Figure 1B) shows the outer glycoprotein shell and inner nucleocapsid shell is connected by the interaction between capsid protein (CP) and cytoplasmic tails of E1 and E2

Summary

Introduction

Getah virus (GETV) is a mosquito-borne RNA virus belonging to the Alphavirus genus in the Togaviridae family, which contains several human pathogens, such as chikungunya virus (CHIKV), Semliki Forest virus (SFV), Venezuelan equine encephalitis virus (VEEV), and Sindbis virus (SINV), etc. Alphaviruses have a global distribution and cause outbreaks in human and animals [1,2,3,4]. As a mosquito-borne virus, GETV has an extensive host range, which includes pig, fox, cattle, horse, and human [9,11,12,13,14]. It usually causes pyrexia, leg oedema in horses [15], stillbirth in pregnant pigs [13], and neurological symptoms and death in piglets [16], leading to economic losses to the livestock industry and posing a threat to public health. There are no licensed vaccines or effective antiviral therapies for most alphaviruses

Methods

Results

Conclusion