Cryo-EM structure of the mature and infective Mayaro virus at 4.4\u2009\xc5 resolution reveals features of arthritogenic alphaviruses

Helder V Ribeiro-Filho,Alexandre Cassago,Lais D Coimbra,João Victor Da Silva Guerra,Luiza Leme,Paulo Sérgio Lopes-De-Oliveira,Adriana F Paes Leme,Daniela B B Trivella,Carolina Moretto Carnieli,Antonio Cláudio Padilha,Rafael Elias Marques,Rafael De Felicio,Rebeca P F Rocha,Rodrigo Villares Portugal

doi:10.1038/s41467-021-23400-9

Helder V Ribeiro-Filho, Alexandre Cassago + Show 12 more

Open Access

https://doi.org/10.1038/s41467-021-23400-9

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Abstract

Mayaro virus (MAYV) is an emerging arbovirus of the Americas that may cause a debilitating arthritogenic disease. The biology of MAYV is not fully understood and largely inferred from related arthritogenic alphaviruses. Here, we present the structure of MAYV at 4.4 Å resolution, obtained from a preparation of mature, infective virions. MAYV presents typical alphavirus features and organization. Interactions between viral proteins that lead to particle formation are described together with a hydrophobic pocket formed between E1 and E2 spike proteins and conformational epitopes specific of MAYV. We also describe MAYV glycosylation residues in E1 and E2 that may affect MXRA8 host receptor binding, and a molecular “handshake” between MAYV spikes formed by N262 glycosylation in adjacent E2 proteins. The structure of MAYV is suggestive of structural and functional complexity among alphaviruses, which may be targeted for specificity or antiviral activity.

Highlights

Mayaro virus (MAYV) is an emerging arbovirus of the Americas that may cause a debilitating arthritogenic disease
The cryo-electron microscopy (cryo-EM) structure of MAYV IQT4235 strain, originally isolated from a symptomatic patient in the Peruvian Amazon, was obtained at a global resolution of 4.4 Å (Supplementary Fig. 1) from a preparation of mature and infectious MAYV propagated in Vero CCL81 cell cultures (PDB entry 7KO8)
EM density map (Supplementary Fig. 3A), even with a lowdensity threshold value, nor in SDS-PAGE gel carried out with the purified MAYV used for cryo-EM data collection (Supplementary Fig. 3B)

Summary

Introduction

Mayaro virus (MAYV) is an emerging arbovirus of the Americas that may cause a debilitating arthritogenic disease. We describe the structure of mature and infective MAYV particles obtained by cryo-EM at 4.4 Å resolution, allowing the observation of N-glycosylation sites in MAYV E1–E2 spikes. A complete list of contacts performed among the MAYV structural proteins is presented in Supplementary Fig. 4.

Results

Conclusion