Structure of Infective Getah Virus at 2.8 Å-resolution Determined by Cryo-EM

Abstract

Getah virus (GETV) is a mosquito-borne pathogen that can cause a mild illness and reproductive losses in animals. Although antibodies to GETV have been found in humans, there are no reports of clinical symptom associated with GETV. However, antivirals or vaccine against GETV is still unavailable due to lack of knowledge of the structure of GETV virion. Here, we present the structure of mature GETV at a resolution of 2.8 Å with capsid protein, envelope glycoproteins E1 and E2. Glycosylation and S-acylation sites in E1 and E2 are identified. The surface-exposed glycans demonstrated their impact on the viral immune evasion and host cell invasion. The S-acylation sites strongly stabilize the virion. In addition, a cholesterol and phospholipid molecule are observed in transmembrane hydrophobic pocket, together with two more cholesterols surround the pocket. These structural information are helpful for structure-based antivirals and vaccine design.

Origin, genetic diversity, adaptive evolution and transmission dynamics of Getah virus

“…The evolution of 262 glycosylation sites may be related to immune escape and budding of the virus. Importantly, this is also mentioned in a preprint study on the structure of GETV (Wang et al, 2021). In domain C, L269Y is in binding surface with the E1 protein, which may affect the interaction between E2 and E1.…”