Understanding the Risk of Bat Coronavirus Emergence Novel zoonotic, bat-origin CoVs are a significant threat to global health and food security, as the cause of SARS in China in 2002, the ongoing outbreak of MERS, and of a newly emerged Swine Acute Diarrhea Syndrome in China. In a previous R01 we found that bats in southern China harbor an extraordinary diversity of SARSr-CoVs, some of which can use human ACE2 to enter cells, infect humanized mouse models causing SARS-like illness, and evade available therapies or vaccines. We found that people living close to bat habitats are the primary risk groups for spillover, that at one site diverse SARSr-CoVs exist that contain every genetic element of the SARS-CoV genome, and identified serological evidence of human exposure among people living nearby. These findings have led to 18 published peer-reviewed papers, including two papers in Nature, and a review in Cell. Yet salient questions remain on the origin, diversity, capacity to cause illness, and risk of spillover of these viruses. In this R01 renewal we will address these issues through 3 specific aims:
Aim 1. Characterize the diversity and distribution of high spillover-risk SARSr-CoVs in bats in southern China. We will use phylogeographic and viral discovery curve analyses to target additional bat sample collection and molecular CoV screening to fill in gaps in our previous sampling and fully characterize natural SARSr-CoV diversity in southern China. We will sequence receptor binding domains (spike proteins) to identify viruses with the highest potential for spillover which we will include in our experimental investigations (Aim 3).
Aim 2. Community, and clinic-based syndromic, surveillance to capture SARSr-CoV spillover, routes of exposure and potential public health consequences. We will conduct biological-behavioral surveillance in high-risk populations, with known bat contact, in community and clinical settings to 1) identify risk factors for serological and PCR evidence of bat SARSr-CoVs; & 2) assess possible health effects of SARSr-CoVs infection in people. We will analyze bat-CoV serology against human-wildlife contact and exposure data to quantify risk factors and health impacts of SARSr-CoV spillover.
Aim 3. In vitro and in vivo characterization of SARSr-CoV spillover risk, coupled with spatial and phylogenetic analyses to identify the regions and viruses of public health concern. We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential. We will combine these data with bat host distribution, viral diversity and phylogeny, human survey of risk behaviors and illness, and serology to identify SARSr-CoV spillover risk hotspots across southern China. Together these data and analyses will be critical for the future development of public health interventions and enhanced surveillance to prevent the re-emergence of SARS or the emergence of a novel SARSr-CoV.

Public Health Relevance

Daszak, Peter Renewal: Understanding the Risk of Bat Coronavirus Emergence Project Narrative Most emerging human viruses come from wildlife, and these represent a significant threat to public health and biosecurity in the US and globally, as was demonstrated by the SARS coronavirus pandemic of 2002-03. This project seeks to understand what factors allow coronaviruses, including close relatives to SARS, to evolve and jump into the human population by studying viral diversity in their animal reservoirs (bats), surveying people that live in high-risk communities in China for evidence of bat-coronavirus infection, and conducting laboratory experiments to analyze and predict which newly-discovered viruses pose the greatest threat to human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI110964-06
Application #
9819304
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Stemmy, Erik J
Project Start
2014-06-01
Project End
2024-06-30
Budget Start
2019-07-24
Budget End
2020-06-30
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Ecohealth Alliance, Inc.
Department
Type
DUNS #
077090066
City
New York
State
NY
Country
United States
Zip Code
10001
Luo, Chu-Ming; Wang, Ning; Yang, Xing-Lou et al. (2018) Discovery of Novel Bat Coronaviruses in South China That Use the Same Receptor as Middle East Respiratory Syndrome Coronavirus. J Virol 92:
Luo, Yun; Li, Bei; Jiang, Ren-Di et al. (2018) Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009-2016. Virol Sin 33:87-95
Zhou, Peng; Fan, Hang; Lan, Tian et al. (2018) Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556:255-258
Wu, Zhiqiang; Lu, Liang; Du, Jiang et al. (2018) Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases. Microbiome 6:178
Wang, Ning; Li, Shi-Yue; Yang, Xing-Lou et al. (2018) Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virol Sin 33:104-107
Eskew, Evan A; Olival, Kevin J (2018) De-urbanization and Zoonotic Disease Risk. Ecohealth 15:707-712
Field, Hume Ernest (2018) Evidence of Australian bat lyssavirus infection in diverse Australian bat taxa. Zoonoses Public Health :
Hu, Ben; Zeng, Lei-Ping; Yang, Xing-Lou et al. (2017) Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 13:e1006698
Olival, Kevin J; Hosseini, Parviez R; Zambrana-Torrelio, Carlos et al. (2017) Host and viral traits predict zoonotic spillover from mammals. Nature 546:646-650
Olival, Kevin J; Willoughby, Anna R (2017) Prioritizing the 'Dormant' Flaviviruses. Ecohealth 14:1-2

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