Scientists identify regions and species driving coronavirus evolution in bats

Scientists identify regions and species driving coronavirus evolution in bats

Scientists are delving deep into bat habitats and discovering how coronaviruses evolve, migrate and jump between species, shedding light on the origins of the pandemic and future risks.

In a study recently published in the journalNature communicationA group of researchers examined the evolution, cross-species transmission and spread of bat coronaviruses (CoVs) in China, identified hotspots of evolutionary diversity and traced the origins of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

background

CoVs are ribonucleic acid viruses (RNA viruses) that cause respiratory and intestinal diseases in humans and animals, with all human-infecting CoVs being of zoonotic origin and often originating from bats. Their large genome size, high recombination rates, and genomic plasticity facilitate cross-species transmission and rapid adaptation, leading to outbreaks such as SARS-CoV, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2. Bats, especially genusRhinolophusharbor diverse alpha-CoVs (α-CoV) and beta-CoVs (β-CoV), with hotspots in regions such as China, where rich bat fauna and unique biogeography increase the risk of spillover. The study highlights that these evolutionary features, combined with the ecological context of southern and southwestern China, make these regions particularly important for understanding CoV dynamics. Further research on the macroevolution and transmission dynamics of bat CoV is crucial to understand the zoonotic potential and improve pandemic prevention through targeted surveillance and preparedness strategies.

About the study

Dynamics of host switching: The study found that alpha coronaviruses (α-CoVs) have a higher propensity for cross-species transmission than beta coronaviruses (β-CoVs), with α-CoVs experiencing host switching between families seven times more frequently. CoVs observed throughout evolution.

In the present study, oral and rectal swabs and fecal pellets were collected from bats in all Chinese provinces, including Anhui, Beijing, Hainan, Hubei, Guangdong, Guangxi, Yunnan, and others, between 2010 and 2015. Non-lethal sampling was carried out using mist nets, with bats released immediately after collection. Wing punches were made for barcode marking with deoxyribonucleic acid (DNA). Bat handling protocols were in accordance with the guidelines of the Institutional Animal Care and Use Committee (IACUC) of Tufts University and the Wuhan Institute of Virology of the Chinese Academy of Sciences. The samples were stored at −80 degrees Celsius.

RNA was extracted using the High Pure Viral RNA Kit (Roche), and a one-step semi-nested reverse transcription-polymerase chain reaction (RT-PCR) targeted the RNA-dependent RNA polymerase gene (RdRp) for CoV detection. PCR products were sequenced and confirmed by cloning or barcoding to ensure data reliability. The dataset included 589 novel sequences and 616 from the Genetic Sequence Database (GenBank) and the Global Initiative on Sharing Avian Influenza Data (GISAID).

Sequences were aligned and phylogenetically analyzed using BEAST (Bayesian Evolutionary Analysis Sampling Trees) software. Based on mammal diversity, sampling locations were divided into six zoogeographic regions. The ancestral states for host family, genus and region were reconstructed and significant host or region transitions were assessed using Bayes factors. The study recognizes that relying on partial RdRp sequences, while effective, limits the depth of phylogenetic analysis and may exclude highly divergent CoV variants.

Phylogenetic diversity metrics revealed regional and host-specific patterns of CoV diversity, with Mantel tests highlighting connections between viral genetic differentiation, host phylogeny and geographical isolation.

Study results

A total of 589 partial sequences of the RdRp gene were generated from bat rectal swabs collected across China and combined with 608 bat CoV and 8 pangolin CoV sequences from public databases including GenBank and GISAID. Two datasets were created: one based on host taxa and the other on sampling locations, categorized into six zoogeographic regions reflecting mammal diversity and non-administrative boundaries. These regions included southwest (SW), north (NE), central (CE), south (SE), central-north (CN), and Hainan Island (HI).

The host dataset contained 676 α-CoV sequences from 40 bat species and 503 β-CoV sequences from 29 bat species. The geographic dataset included sequences from 21 provinces for α-CoVs and 20 provinces for β-CoVs. Analyzes were also performed on random subsets of sequences to reduce sampling bias and ensure consistent representation.

Phylogenetic clustering: Strong phylogenetic clustering was found among bat families with different developmental patterns in southern and southwestern China. Regions such as Hainan Island showed unique endemic CoV diversity.

Bayesian phylogenetic analysis suggested that α-CoVs likely originated inrhino(horseshoe bat) andVespertilionide(evening bats) species, while β-CoVs have been linked to itVespertilionideAndPterosaurs(Flying foxes) species. Cross-species transmission events were frequently observed, with α-CoVs exhibiting higher rates of host switching between families and genera compared to β-CoVs. Rhinolophidae and Miniopteridae (long-fingered bats) were the most common donors of α-CoVs, whereasRhinolophidaedominate as donors and recipients for β-CoVs.

Spatiotemporal analyzes revealed significant propagation routes for both α-CoVs and β-CoVs within China. The SO emerged as a major center of CoV migration with the highest outbound and inbound movements. α-CoVs showed higher migration rates than β-CoVs, with the SW and HI regions showing pronounced endemic diversity. Southern and southwestern China were identified as refugia during the ice ages, contributing to the long-term persistence and diversification of bat CoVs in these regions.

Phylogenetic clustering, assessed by mean phylogenetic distance (MPD) and mean distance to nearest taxon (MNTD), showed strong structuring between bat families and zoogeographic regions. The SW and HI regions showed the highest evolutionary distinctness for both CoV genera. Mantel tests revealed significant correlations between genetic differentiation and geographic distance for both α-CoVs and β-CoVs, with β-CoVs also showing correlations with host phylogeny.

Conclusions

Phylogenetic analysis of CoVs from bats sampled in China revealed significant diversity: 11 out of 17 bat genera harbored both α-CoVs and β-CoVs. SARS-CoV-2 likely comes from a group of viruses found in horseshoe bats (Rhinolophus spp.), mainly in Yunnan Province. However, the study notes that restrictions on sampling and the proximity of collection sites to international borders suggest that precursor viruses could also have originated in Myanmar, Laos or other neighboring countries.

The results highlight the urgent need for targeted surveillance in southern China and Southeast Asia, with a particular focus on thisRhinolophusAndHipposiderosBats, which are central to cross-species transmission events. The study also emphasizes the importance of understanding the biological properties of α-CoVs, which have higher host switching potential and zoonotic risk than β-CoVs.

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