Early Genomic Surveillance and Phylogeographic Analysis of Getah Virus, a Reemerging Arbovirus, in Livestock in China.

Jin Zhao1,2 Simon Dellicour3,4 Ziqing Yan1 Michael Veit5 Mandev S Gill6,7 Wan-Ting He1,2,4 Xiaofeng Zhai1,2 Xiang Ji8 Marc A Suchard9,10,11 Philippe Lemey4 Shuo Su1,2
Affiliations 11 institutions
  1. Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  2. Sanya Institute of Nanjing Agricultural University, Sanya, China.
  3. Spatial Epidemiology Lab (SpELL), Université Libre de Bruxelles, Brussels, Belgium.
  4. Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory for Clinical and Epidemiological Virology, KU Leuven, Leuven, Belgium.
  5. Institute for Virology, Center for Infection Medicine, Veterinary Faculty, Free University Berlin, Berlin, Germany.
  6. Department of Statistics, University of Georgia, Athens, Georgia, USA.
  7. Institute of Bioinformatics, University of Georgia, Athens, Georgia, USA.
  8. Department of Mathematics, School of Science & Engineering, Tulane University, New Orleans, Louisiana, USA.
  9. Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA.
  10. Department of Biomathematics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  11. Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

Abstract

Getah virus (GETV) mainly causes disease in livestock and may pose an epidemic risk due to its expanding host range and the potential of long-distance dispersal through animal trade. Here, we used metagenomic next-generation sequencing (mNGS) to identify GETV as the pathogen responsible for reemerging swine disease in China and subsequently estimated key epidemiological parameters using phylodynamic and spatially-explicit phylogeographic approaches. The GETV isolates were able to replicate in a variety of cell lines, including human cells, and showed high pathogenicity in a mouse model, suggesting the potential for more mammal hosts. We obtained 16 complete genomes and 79 E2 gene sequences from viral strains collected in China from 2016 to 2021 through large-scale surveillance among livestock, pets, and mosquitoes. Our phylogenetic analysis revealed that three major GETV lineages are responsible for the current epidemic in livestock in China. We identified three potential positively selected sites and mutations of interest in E2, which may impact the transmissibility and pathogenicity of the virus. Phylodynamic inference of the GETV demographic dynamics identified an association between livestock meat consumption and the evolution of viral genetic diversity. Finally, phylogeographic reconstruction of GETV dispersal indicated that the sampled lineages have preferentially circulated within areas associated with relatively higher mean annual temperature and pig population density. Our results highlight the importance of continuous surveillance of GETV among livestock in southern Chinese regions associated with relatively high temperatures. IMPORTANCE Although livestock is known to be the primary reservoir of Getah virus (GETV) in Asian countries, where identification is largely based on serology, the evolutionary history and spatial epidemiology of GETV in these regions remain largely unknown. Through our sequencing efforts, we provided robust support for lineage delineation of GETV and identified three major lineages that are responsible for the current epidemic in livestock in China. We further analyzed genomic and epidemiological data to reconstruct the recent demographic and dispersal history of GETV in domestic animals in China and to explore the impact of environmental factors on its genetic diversity and its diffusion. Notably, except for livestock meat consumption, other pig-related factors such as the evolution of live pig transport and pork production do not show a significant association with the evolution of viral genetic diversity, pointing out that further studies should investigate the potential contribution of other host species to the GETV outbreak. Our analysis of GETV demonstrates the need for wider animal species surveillance and provides a baseline for future studies of the molecular epidemiology and early warning of emerging arboviruses in China.

Supporting text Virus Host Location
genomic surveillance 10 Getah virus 5 next-generation sequencing 7 phylodynamics 7 phylogeography 35 zoonotic pathogens 4 Arboviruses 6 Genome, Viral 317 Phylogeny 805 Animals 1949 China 229 Genomics 32 Humans 1441 Livestock 20 Mice 253

Evidence records

6 total
Zoonotic Surveillance
3 records · 2 evidence types
Evidence type
2 records
OVE6561
Key finding

Getah virus (GETV) was detected in swine in China using metagenomic next-generation sequencing.

Virus
Host
Location
Supporting text

we used metagenomic next-generation sequencing (mNGS) to identify GETV as the pathogen responsible for reemerging swine disease in China

Method
metagenomic next-generation sequencing (mNGS)
Sample type
swine disease samples
Geographic raw
China
Country inferred
CHN
OVE6562
Key finding

Getah virus (GETV) genomes and E2 gene sequences were detected in surveillance samples from livestock, pets, and mosquitoes in China between 2016 and 2021.

Virus
Host
Location
Supporting text

We obtained 16 complete genomes and 79 E2 gene sequences from viral strains collected in China from 2016 to 2021 through large-scale surveillance among livestock, pets, and mosquitoes

Method
genome sequencing | E2 gene sequencing
Sample type
surveillance samples
Geographic raw
China
Country inferred
CHN
Evidence type
1 records
OVE6567
Key finding

Livestock are described as the primary reservoir host of Getah virus (GETV) in Asian countries.

Virus
Host
Not specified
Location
Supporting text

Although livestock is known to be the primary reservoir of Getah virus (GETV) in Asian countries, where identification is largely based on serology.

Method
serology
Sample type
serology
Geographic raw
Asian countries
Experimental Infection
1 records · 1 evidence types
Evidence type
1 records
OVE6564
Key finding

Getah virus (GETV) isolates exhibited high pathogenicity when experimentally tested in a mouse model.

Virus
Host
Location
Not specified
Supporting text

The GETV isolates were able to replicate in a variety of cell lines, including human cells, and showed high pathogenicity in a mouse model.

Method
experimental infection in mouse model | assessment of disease phenotype or severity
Experimental system
mouse model
Functional Mechanism
1 records · 1 evidence types
Evidence type
1 records
OVE6566
Key finding

Three positively selected sites and mutations in the Getah virus E2 gene may contribute to adaptation affecting its transmissibility and pathogenicity.

Virus
Host
Not specified
Location
Not specified
Supporting text

We identified three potential positively selected sites and mutations of interest in E2, which may impact the transmissibility and pathogenicity of the virus.

Genes or proteins
E2
Mechanism types
transmission fitness | virulence adaptation
Genomic Evolution
1 records · 1 evidence types
Evidence type
1 records
OVE6565
Key finding

Phylogenetic analysis identified three major Getah virus (GETV) lineages driving the current epidemic in livestock in China.

Virus
Host
Not specified
Location
Not specified
Supporting text

Our phylogenetic analysis revealed that three major GETV lineages are responsible for the current epidemic in livestock in China.

Genes or proteins
E2 gene | complete genomes
Analysis methods
phylogenetic analysis