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Bat cave study sheds new light on origin of SARS virus

Newly discovered SARS strains in bats hold genetic clues to the evolution of a human pandemic strain

PLOS

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IMAGE: This is the side face of a Chinese horseshoe bat (Rhinolophus sinicus). view more 

Credit: Photo by Dr. Libiao Zhang from Guangdong Institute of Applied Biological Resource, China

Genetic recombination between viral strains in bats may have produced the direct evolutionary ancestor of the strain that caused a deadly outbreak of severe acute respiratory syndrome (SARS) in humans, according to new research published in PLOS Pathogens.

In late 2002, a SARS pandemic broke out in southern China, ultimately killing hundreds of people in dozens of countries by the summer of 2003. Scientists traced the outbreak back to horseshoe bats, hypothesizing that the culprit, SARS coronavirus, originated in these animals and then spread either directly to humans or to animals later purchased by humans at markets.

However, the details of the outbreak's origin remain unclear. SARS strains found in bats are genetically distinct from the specific SARS strain that caused the outbreak, suggesting that known bat strains did not directly evolve into the outbreak strain.

To address this issue, Ben Hu of the Chinese Academy of Sciences in Wuhan, China, and colleagues spent five years studying SARS viruses found in multiple species of horseshoe bats living in a single cave in Yunnan Province, China. In the new study, the researchers identified 11 new strains of SARS virus and sequenced their full genomes to uncover their evolutionary relationships.

Genome analysis revealed that the newly identified bat strains, as well as several strains identified in a previous study of the same bat cave, contained all the essential genetic building blocks of the human SARS coronavirus. In some of the strains, for instance, portions of a gene known as the S gene showed high genetic similarity to the same regions found in the SARS coronavirus genome.

Based on their genetic analysis, the researchers hypothesize that genetic recombination between precursor strains that later evolved into the newly identified strains may also have given rise to a strain that directly evolved into SARS coronavirus.

Additional lab experiments showed that some of the newly identified bat strains are capable of entering human cells via the same cellular receptor employed by SARS coronavirus. This suggests that the bat cave contains strains that could potentially be directly transmitted to humans.

Overall, these findings provide new insights into the evolutionary origin of SARS coronavirus. Because of the potential risk of existing bat strains spreading to humans, the researchers propose continued monitoring of the cave they studied, as well as other sites that may pose similar risk.

"Rhinolophus bats in China harbor genetically diverse SARS-related coronaviruses," the authors explain, "which may have given rise to the direct progenitor of SARS coronavirus after recombination."

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In your coverage please use this URL to provide access to the freely available article in PLOS Pathogens: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006698

Citation: Hu B, Zeng L-P, Yang X-L, Ge X-Y, Zhang W, Li B, 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(11): e1006698. https://doi.org/10.1371/journal.ppat.1006698

Funding: This work was jointly funded by National Natural Science Foundation of China (81290341, 31621061) to ZLS, China Mega-Project for Infectious Disease (2014ZX10004001-003) to ZLS, Scientific and technological basis special project (2013FY113500) to YZZ and ZLS from the Ministry of Science and Technology of China, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDPB0301) to ZLS, the National Institutes of Health (NIAID R01AI110964), the USAID Emerging Pandemic Threats (EPT) PREDICT program to PD and ZLS, CAS Pioneer Hundred Talents Program to JC, NRF-CRP grant (NRF-CRP10-2012-05) to LFW and WIV "OneThree-Five" Strategic Program (WIV-135-TP1) to JC and ZLS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

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