Biology subjects

Ar Gouilh, M.

Publications and source records attributed to Ar Gouilh, M..

4 recordsLinked to original sources

bioRxiv2026

A 10-year longitudinal study reveals bat-driven SARSr-CoV evolution

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.

microbiology↗

bioRxiv2024

SARS-CoV-2 Delta variant induces severe damages in the nasal cavity from the first day post-infection in the Syrian hamster model.

SARS-CoV-2 replication initiates in the nasal cavity and can spread to the lower respiratory tract. However, the early physiopathological events that occur in the nasal cavity after infection remain poorly understood. In this study, we investigated the initial steps of viral infection from 1 day post-infection (dpi) in Syrian hamsters infected with SARS-CoV-2 D614G, Delta and Omicron (BA.1) variants and compared them with animals sacrificed at 4 dpi. While the level of viral replication in the nasal turbinates of the three groups of hamsters was equivalent at 4dpi, the amount of viral RNA at 1dpi was higher in D614G- and Delta-infected animals than in the Omicron group. No difference in viral RNA levels or inflammatory markers in the nasal turbinates was observed between D614G- and Delta-infected animals, except for a significantly higher level of IFN-{lambda} in the Delta group at 1dpi. Additionally, histological analysis revealed a more rapid diffusion of the Delta virus reaching the posterior zone of the nasal cavity at 1dpi inducing significant damage to the olfactory epithelium. At the same time, the D614G and Omicron infections were essentially restricted to the anterior part of the nasal cavity with less damage observed. Consistently, viral replication was already effective in the lungs of all Delta- infected hamsters at 1 dpi, but only in two of the six D614G animals. Our results highlight the importance of studying viral infection in the nasal cavity very early after infection with a spatial approach to better understand the physiopathology of the different SARS-CoV-2 variants.

microbiology↗

bioRxiv2020

High prevalence of SARS-CoV-2 antibodies in pets from COVID-19+ households

In a survey of household cats and dogs of laboratory-confirmed COVID-19 patients, we found a high seroprevalence of SARS-CoV-2 antibodies, ranging from 21% to 53%, depending on the positivity criteria chosen. Seropositivity was significantly greater among pets from COVID-19+ households compared to those with owners of unknown status. Our results highlight the potential role of pets in the spread of the epidemic.

microbiology↗

bioRxiv2020

Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

neuroscience↗