Structure of infective Getah virus at 2.8 A\u030a resolution determined by cryo-electron microscopy

Aojie Wang,Sheng Liu,Dongsheng Gao,Yinhe Xia,Lutang Fu,Congcong Liu,Yawei Xu,Feng Zhou,Yuanzhu Gao,Yiheng Yin,Zheng Liu,Ruxi Qi,Chuanqing Wang

doi:10.1038/s41421-022-00374-6

Abstract

Getah virus (GETV), a member of the genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptoms associated with GETV. The biological and pathological properties of GETV are largely unknown and antiviral or vaccine treatments against GETV are still unavailable due to a lack of knowledge of the structure of the GETV virion. Here, we present the structure of infective GETV at a resolution of 2.8 Å with the atomic models of the capsid protein and the envelope glycoproteins E1 and E2. We have identified numerous glycosylation and S-acylation sites in E1 and E2. The surface-exposed glycans indicate a possible impact on viral immune evasion and host cell invasion. The S-acylation sites might be involved in stabilizing the transmembrane assembly of E1 and E2. In addition, a cholesterol and a phospholipid molecule are observed in a transmembrane hydrophobic pocket, together with two more cholesterols surrounding the pocket. The cholesterol and phospholipid stabilize the hydrophobic pocket in the viral envelope membrane. The structural information will assist structure-based antiviral and vaccine screening, design, and optimization.

Highlights

Getah virus (GETV) is a mosquito-borne arbovirus, and belongs to the Semliki Forest group of the Alphavirus genus within the Togaviridae family[1]
Total RNA was extracted from tissues, including spleen, lung, cerebral cortex, and various lymph nodes at 5 days postinoculation (DPI), and subjected to RT-PCR for GETV detection (Supplementary Fig. S1g, h)
Glycosylation is known to be a key determinant of cellular tropism and virulence: a lack of glycosylation in Ross River virus (RRV) renders virions unable to induce alpha/beta interferon production in myeloid dendritic cells, the professional antigenpresenting cells that rapidly respond to viruses, suggesting that viral glycans may negatively regulate antiviral responses[54]

Summary

Introduction

Getah virus (GETV) is a mosquito-borne arbovirus, and belongs to the Semliki Forest group of the Alphavirus genus within the Togaviridae family[1]. Alongside GETV, members in the Semliki Forest Group include Chikungunya virus (CHIKV), Semliki Forest virus (SFV), Mayaro virus (MAYV), Una virus (UNAV), Bebaru virus (BEBV), and O’nyong-nyong virus (ONNV). GETV was first isolated in Malaysia in 1955 from Culex gelidus mosquitoes[5], and was found to have a worldwide among racehorses occurred in Japan in 1978 and outbreaks have re-emerged several times since in Japan and India[6,7]. GETV has been isolated from newborn piglets that died of acute disease and dead fetuses removed from infected sows in Japan[9,10]. The emergence of GETV in China was found in 2017 in swine farms, resulting in the death of the newborn piglets 5–10 days after birth and in pregnant sows exhibiting stillbirths or fetal mummies[11].

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Results

Conclusion