A 10-year longitudinal study reveals bat-driven SARSr-CoV evolution
- 1Biology & Earth Sciences Department, U1311 Inserm, Dynamicure, Unirouen, University of Caen Normandy, Caen, France | Virology Department, Caen University Hospit
Abstract
Bats are recognized reservoirs for several zoonoses and have an exceptional tolerance to viruses, likely linked with strong evolutionary selection in immune genes. Notably, in light of the emergence history of severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 is hypothesized to have originated from Rhinolophus bats as well. In-depth studies are still needed, however, to unravel how SARS-related coronaviruses (SARSr-CoVs) persist and thrive in nature through evolution, virus-host interactions, and cross-species transmission. Here we present a pioneering 10-year longitudinal study of BBCoV-EPI1, a SARSr-CoV in Rhinolophus bats that revealed the complexity of virus-host interactions and the tempo at which new viral lineages emerge. Our results demonstrated the impacts of host life cycles (hibernation, female gathering, weaning juveniles, and mating periods) on strong seasonal oscillations in viral prevalence. These pronounced fluctuations drove viral diversification through bottlenecks, founder effects and Darwinian selection, counterbalanced by high mutation rates, fast gradualism, and recombination. We also found that host-cell enzymes are major contributors to BBCoV-EPI1 evolution in bats. The antiviral effect of APOBEC3 detected here in bats is weaker than it is in humans. Conversely, the ADAR enzyme had an unexpectedly strong and beneficial influence on viral evolution, even though the high mutation rate of RNA viruses is usually attributed to viral polymerases' low replication fidelity. We discovered that key BBCoV-EPI1 innovations in Rhinolophus bats were mostly located in proteins involved in cell-cycle hijack and in blocking bat cells' antiviral response, rather than in the Spike (S). We also showed that the BBCoV-EPI1 S protein efficiently uses angiotensin-converting enzyme 2 (ACE2) receptor to enter Rhinolophus bat cells, but not to enter human or sympatric species cells, due to amino-acid differences at the S-ACE2 interface. Last, this work identifies 101 critical amino-acid changes frequently associated with viral fitness shift, and paves the way for future experimental studies focusing on the capacity of SARSr-CoVs to adapt to hosts and cross the species barrier.
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BibTeX
@misc{fonclare202610year,
title = {{A 10-year longitudinal study reveals bat-driven SARSr-CoV evolution}},
author = {D. de Riols de Fonclare and A. Szczepanski and A. Milewska and S. Corbet and L. Rouilly and L. Diancourt and B. Elie and S. Lequime and B. Leterrier and S. J. Puechmaille and F. Touzalin and E. Decroly and A. Vabret and S. Le Poder and K. Pyrc and M. Ar Gouilh},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.754022},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.754022v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A 10-year longitudinal study reveals bat-driven SARSr-CoV evolution
AU - D. de Riols de Fonclare
AU - A. Szczepanski
AU - A. Milewska
AU - S. Corbet
AU - L. Rouilly
AU - L. Diancourt
AU - B. Elie
AU - S. Lequime
AU - B. Leterrier
AU - S. J. Puechmaille
AU - F. Touzalin
AU - E. Decroly
AU - A. Vabret
AU - S. Le Poder
AU - K. Pyrc
AU - M. Ar Gouilh
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.754022
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.754022v1
AB - Bats are recognized reservoirs for several zoonoses and have an exceptional tolerance to viruses, likely linked with strong evolutionary selection in immune genes. Notably, in light of the emergence history of severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 is hypothesized to have originated from Rhinolophus bats as well. In-depth studies are still needed, however, to unravel how SARS-related coronaviruses (SARSr-CoVs) persist and thrive in nature through evolution, virus-host interactions, and cross-species transmission. Here we present a pioneering 10-year longitudinal study of BBCoV-EPI1, a SARSr-CoV in Rhinolophus bats that revealed the complexity of virus-host interactions and the tempo at which new viral lineages emerge. Our results demonstrated the impacts of host life cycles (hibernation, female gathering, weaning juveniles, and mating periods) on strong seasonal oscillations in viral prevalence. These pronounced fluctuations drove viral diversification through bottlenecks, founder effects and Darwinian selection, counterbalanced by high mutation rates, fast gradualism, and recombination. We also found that host-cell enzymes are major contributors to BBCoV-EPI1 evolution in bats. The antiviral effect of APOBEC3 detected here in bats is weaker than it is in humans. Conversely, the ADAR enzyme had an unexpectedly strong and beneficial influence on viral evolution, even though the high mutation rate of RNA viruses is usually attributed to viral polymerases' low replication fidelity. We discovered that key BBCoV-EPI1 innovations in Rhinolophus bats were mostly located in proteins involved in cell-cycle hijack and in blocking bat cells' antiviral response, rather than in the Spike (S). We also showed that the BBCoV-EPI1 S protein efficiently uses angiotensin-converting enzyme 2 (ACE2) receptor to enter Rhinolophus bat cells, but not to enter human or sympatric species cells, due to amino-acid differences at the S-ACE2 interface. Last, this work identifies 101 critical amino-acid changes frequently associated with viral fitness shift, and paves the way for future experimental studies focusing on the capacity of SARSr-CoVs to adapt to hosts and cross the species barrier.
ER -