Biology subjects

Dacheux, L.

Publications and source records attributed to Dacheux, L..

3 recordsLinked to original sources

bioRxiv2024

Antiviral activity of Tecovirimat against Mpox virus clades 1a, 1b, 2a and 2b

The recent Mpox virus (MPXV) outbreak was caused by a novel and more pathogenic clade 1b virus. We compared the antiviral efficacy of Tecovirimat in cell culture, against the two ancestral clades 1a and 2a, the clade 2b that circulated in 2022, and the recent clade 1b virus. We report that Tecovirimat similarly inhibits the replication of all four MPXV clades, at nanomolar concentrations (nM). Our results suggest that Tecovirimat remains a therapeutic option against the latest clade 1b virus.

microbiology↗

bioRxiv2024

Large circulation of a novel vesiculovirus in bats in the Mediterranean region

Bats are the natural reservoirs of a variety of emerging or re-emerging viruses. Among them, rabies virus (genus Lyssavirus, family Rhabdoviridae) is of the first and most iconic described in these animals. Since its first description, various new bat lyssaviruses have been regularly described. Apart from lyssaviruses, other bat rhabdoviruses have been also identified, including members of the Vesiculovirus, Ledantevirus and more recently Alphanemrhavirus and Tupavirus genera. However, the family Rhabdoviridae is one of the most abundant and diverse viral families, with 318 officially recognized species divided into 3 subfamilies and 46 different genera. Thus, the number of bat- associated rhabdoviruses is probably higher. In this study, we first developed and validated a combined nested RT-qPCR technique (pan-rhabdo RT-nqPCR) dedicated to the broad detection of animal rhabdovirus. After validation, this technique was used for a large retrospective screening of archival bat samples (n = 1962), including blood (n = 816), brain (n = 723) and saliva (n = 423). These samples were collected from various bat species over a period of 12 years (2007-2019) in 9 different countries in Europe and Africa. A total of 23 samples (1.2%) from Miniopterus schreibersii, Rhinolophus euryale and Rhinolophus ferrumequinum bat species was found positive for rhabdovirus infection, including 17 (2.1%) blood and 6 (1.4%) saliva samples, all collected from bats originated from the Mediterranean region. The complete virus genome sequences were obtained by next-generation sequencing for most of the positive samples. Molecular and phylogenetic analysis of these sequences demonstrated that these virus isolates, named Mediterranean bat virus (MBV), were closely related, and represented a new species Vesiculovirus mediterranean within the Vesiculovirus genus. MBV was more specifically related to the other bat vesiculoviruses previously described in China and North America, together clustering into a distinct group of bat viruses within this genus. Interestingly, our results suggest that MBV is widely distributed, at least in the West part of the Mediterranean region, where it can act as an arbovirus infecting and circulating in multiple bat species. These findings expand the host range and the viral diversity of bat vesiculoviruses and pave the way for further investigations to determine the route of transmission and the dynamic of diffusion of these viruses into bat colonies, as well as to evaluate their potential hazard for public health.

microbiology↗

bioRxiv2021

Species-specific molecular barriers to SARS-CoV-2 replication in bat cells

Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the susceptibility of primary cells from Rhinolophus ferrumequinum and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis and Nyctalus noctula, to SARS-CoV-2 infection. None of these cells were sensitive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication. This ability to control viral replication correlated with a potent interferon response. Our data highlight the existence of species-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses. Author summaryBats host ancestors of several viruses that cause serious disease in humans, as illustrated by the on-going SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions have been hampered by a limited number of bat cell lines. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The varying susceptibilities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by over-expression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bats and viruses.

microbiology↗