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

Abstract

As a member of the Alphavirus, Getah virus (GETV) was becoming more serious and posing a serious threat to animal safety and public health. However, the circulation, distribution and evolution of GETV is not well understood. Hence, we integrated a variety of bioinformatic methodologies, from genomic alterations to systematic analysis, phylogeography, selection, adaptive analysis, prediction of protein modification, structural biology and molecular dynamics simulations to understand the characteristics of GETV. The results of phylogeography and molecular evolution show that due to the lack of vaccine, GETV is rapidly expanding its host range and geographical distribution at a high evolutionary rate. We also predicted the important modification sites, and identified the adaptive and active selection sites. Finally, the analysis of spatial structure and function showed that six adaptive sites may be related to the structural stability, receptor binding ability, immunogenicity and immune evasion of the virus, respectively. The data from this study have important implications for the understanding of ongoing GETV outbreaks worldwide and will guide future efforts to develop effective preventive and control measures against GETV. In particular, biosafety measures should be strengthened immediately to prevent GETV from becoming a pandemic, especially in China, South Korea and Japan.

Development and application of an indirect ELISA for detecting equine IgG antibodies against Getah virus with recombinant E2 domain protein

“…With its wide geographic distribution and strong host adaptation as shown in one of our previous reports (Shi et al, 2021), GETV disease has been seriously jeopardizing the healthy development of the horse and pig industries in China and even the world, causing large losses to the livestock industry and posing an increasing potential threat to public health security. Up to now, GETV disease outbreaks in equine herds six times worldwide, among which, five times occurred in Japan and one time in India.…”

“…Notably, the structural protein encoded by the E gene not only constitutes the surface protrusion of the viral particle, but is the critical protein for the adsorption of GETV virus to target cells and the induction of anti-infection immunity in the host ( Voss et al, 2010 ). Based on the evolutionary analysis of the nucleotide sequence of the E2 gene or whole genome, GETV strains can be divided into four groups I–IV, and most of the strains prevalent in the world after 1964 belong to group III ( Li et al, 2017 ; Shi et al, 2021 ). As a re-emerging mosquito-borne disease, GETV disease is an increasingly prominent epidemic problem in China.…”

Establishment of a reverse transcription real-time quantitative PCR method for Getah virus detection and its application for epidemiological investigation in Shandong, China

“…In contrast, GETV is an arbovirus with a broad spectrum of infection, and an RT-qPCR assay that can be applied to multiple species of swine, horses, bovines, sheep, and mosquitoes is of more practical application. One study performed multiple sequence alignment analysis and phylogenetic analysis of 45 whole-genome sequences, 71 E2, 47 E1, 61 Nsp1, and 57 Cap gene sequences of GETV from NCBI and found that the Nsp1 gene was the most stable and had the lowest mutation rate during the evolution of GETV transmission (Shi et al, 2021). In this study, specific primers were designed based on the conserved sequence of Nsp1 of GETV, and after optimization, the method was found to have excellent specificity, with a specific melting peak at 85.5 ± 0.5°C.…”

“…In addition, the identification of neutralizing antibodies against GETV from human serum showed that the antibody titers in fever patients were significantly higher than that of healthy individuals (Hu et al, 2012). As a widespread arbovirus, the epidemic scope and host numbers of GETV are expanding (Shi et al, 2021). What's more, in China, the transmission of GETV has been detected in 18 provinces so far (Lu et al, 2020), which has already caused serious economic losses to local farms.…”

LDLR is used as a cell entry receptor by multiple alphaviruses

“…Notably, GETV infection has been reported in different mammalian orders other than their perceived reservoir host groups 25 . Therefore, although MXRA8 has been identified as a receptor for GETV, the rather limited expression profiles of MXRA8 in several tissues cannot explain the ability of GETV to infect large numbers of species and tissues 17 , 23 , 26 . It remained unknown whether receptors identified for other alphaviruses or some unknown receptors facilitate the cell entry of GETV 27 .…”