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Science Advances Jun 2023Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome...
Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect the brain and are associated with severe neurological symptoms through poorly understood mechanisms. We show that SARS-CoV-2 infection induces fusion between neurons and between neurons and glia in mouse and human brain organoids. We reveal that this is caused by the viral fusogen, as it is fully mimicked by the expression of the SARS-CoV-2 spike (S) protein or the unrelated fusogen p15 from the baboon orthoreovirus. We demonstrate that neuronal fusion is a progressive event, leads to the formation of multicellular syncytia, and causes the spread of large molecules and organelles. Last, using Ca imaging, we show that fusion severely compromises neuronal activity. These results provide mechanistic insights into how SARS-CoV-2 and other viruses affect the nervous system, alter its function, and cause neuropathology.
Topics: Animals; Humans; Mice; COVID-19; SARS-CoV-2; Neurons; Brain; Neuroglia
PubMed: 37285437
DOI: 10.1126/sciadv.adg2248 -
Nature Microbiology Aug 2022Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins...
Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins has piqued interest in the viromes of these wild, scaly-skinned mammals. We sequenced the viromes of 161 pangolins that were smuggled into China and assembled 28 vertebrate-associated viruses, 21 of which have not been previously reported in vertebrates. We named 16 members of Hunnivirus, Pestivirus and Copiparvovirus pangolin-associated viruses. We report that the L-protein has been lost from all hunniviruses identified in pangolins. Sequences of four human-associated viruses were detected in pangolin viromes, including respiratory syncytial virus, Orthopneumovirus, Rotavirus A and Mammalian orthoreovirus. The genomic sequences of five mammal-associated and three tick-associated viruses were also present. Notably, a coronavirus related to HKU4-CoV, which was originally found in bats, was identified. The presence of these viruses in smuggled pangolins identifies these mammals as a potential source of emergent pathogenic viruses.
Topics: Animals; COVID-19; Chiroptera; Humans; Mammals; Pangolins; SARS-CoV-2
PubMed: 35918420
DOI: 10.1038/s41564-022-01181-1 -
Cells May 2022Mammalian orthoreoviruses (ReoV) are non-enveloped viruses with segmented double-stranded RNA genomes. In humans, ReoV are generally considered non-pathogenic, although... (Review)
Review
Mammalian orthoreoviruses (ReoV) are non-enveloped viruses with segmented double-stranded RNA genomes. In humans, ReoV are generally considered non-pathogenic, although members of this family have been proven to cause mild gastroenteritis in young children and may contribute to the development of inflammatory conditions, including Celiac disease. Because of its low pathogenic potential and its ability to efficiently infect and kill transformed cells, the ReoV strain Type 3 Dearing (T3D) is clinical trials as an oncolytic agent. ReoV manifests its oncolytic effects in large part by infecting tumor cells and activating programmed cell death pathways (PCDs). It was previously believed that apoptosis was the dominant PCD pathway triggered by ReoV infection. However, new studies suggest that ReoV also activates other PCD pathways, such as autophagy, pyroptosis, and necroptosis. Necroptosis is a caspase-independent form of PCD reliant on receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and its substrate, the pseudokinase mixed-lineage kinase domain-like protein (MLKL). As necroptosis is highly inflammatory, ReoV-induced necroptosis may contribute to the oncolytic potential of this virus, not only by promoting necrotic lysis of the infected cell, but also by inflaming the surrounding tumor microenvironment and provoking beneficial anti-tumor immune responses. In this review, we summarize our current understanding of the ReoV replication cycle, the known and potential mechanisms by which ReoV induces PCD, and discuss the consequences of non-apoptotic cell death-particularly necroptosis-to ReoV pathogenesis and oncolysis.
Topics: Animals; Apoptosis; Cell Death; Child; Child, Preschool; Humans; Mammals; Necroptosis; Necrosis; Protein Kinases
PubMed: 35681452
DOI: 10.3390/cells11111757 -
Virologie (Montrouge, France) Jun 2023As the world is experiencing the pandemic of SARS-CoV-2 responsible for COVID-19, one can wonder if members of other family of viruses could possibly emerge. Can such... (Review)
Review
As the world is experiencing the pandemic of SARS-CoV-2 responsible for COVID-19, one can wonder if members of other family of viruses could possibly emerge. Can such viruses establish a worldwide distribution with consequences similar to SARS-CoV-2? One such threat is the possible emergence of pathogenic reoviruses, especially by zoonotic transmission. Reoviruses are ubiquitous viruses exhibiting a worldwide distribution and various strains or isolates are found in many mammalian species and other vertebrates. When initially discovered, these viruses were named respiratory enteric orphan viruses (hence the acronym "reo") in order to reflect the fact that they could not be clearly associated with any given disease. However, this is not necessarily the case for all of these viruses, as clearly shown for some of these in animals. Significantly, there have been numerous reports of zoonotic transmission, especially from bats to humans. In this manuscript, pertinent properties of reoviruses will be first briefly presented followed by a review of available evidence for zoonotic transmission of pathogenic reoviruses to humans. Future work that appears to be needed for preparedness to the possible emergence of these viruses will then be briefly discussed.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Pandemics; Viruses; Orthoreovirus; Chiroptera
PubMed: 37476988
DOI: 10.1684/vir.2023.1009 -
Journal of Fish Diseases Nov 2020Piscine orthoreovirus (PRV) is a common and widely distributed virus of salmonids. Since its discovery in 2010, the virus has been detected in wild and farmed stocks... (Review)
Review
Piscine orthoreovirus (PRV) is a common and widely distributed virus of salmonids. Since its discovery in 2010, the virus has been detected in wild and farmed stocks from North America, South America, Europe and East Asia in both fresh and salt water environments. Phylogenetic analysis suggests three distinct genogroups of PRV with generally discrete host tropisms and/or regional patterns. PRV-1 is found mainly in Atlantic (Salmo salar), Chinook (Oncorhynchus tshawytscha) and Coho (Oncorhynchus kisutch) Salmon of Europe and the Americas; PRV-2 has only been detected in Coho Salmon of Japan; and PRV-3 has been reported primarily in Rainbow Trout (Oncorhynchus mykiss) in Europe. All three genotypes can establish high-load systemic infections by targeting red blood cells for principal replication. Each genotype has also demonstrated potential to cause circulatory disease. At the same time, high-load PRV infections occur in non-diseased salmon and trout, indicating a complexity for defining PRV's role in disease aetiology. Here, we summarize the current body of knowledge regarding PRV following 10 years of study.
Topics: Animals; Aquaculture; Fish Diseases; Genotype; Orthoreovirus; Phylogeny; Reoviridae Infections; Salmon; Trout
PubMed: 32935367
DOI: 10.1111/jfd.13228 -
Avian Diseases Dec 2022Viral arthritis/tenosynovitis, a disease caused by avian reovirus (ARV), leads to great economic losses for the chicken industry worldwide. Since autumn 2011, the... (Review)
Review
Viral arthritis/tenosynovitis, a disease caused by avian reovirus (ARV), leads to great economic losses for the chicken industry worldwide. Since autumn 2011, the poultry industries in the United States and Canada have sustained significant economic losses in the progeny of broiler breeders vaccinated with classic strains of ARV. Vaccination failure has been caused by field challenge with variant ARVs. The variant field ARVs are refractory to the immunity stimulated by classic vaccines and have become the prevalent challenge in the field. Because all genotypes described in the literature have been reported to be circulating in Canada, genotyping of circulating ARVs is paramount for the selection of appropriate isolates, representative of the field challenge, for use in autogenous vaccines. In this review, the history of ARVs and the current situation in Canada are discussed. On the basis of recent field data, inadequate measures commonly used in the field are discussed, and successful vaccination strategies are recommended.
Topics: Animals; Chickens; Reoviridae Infections; Poultry Diseases; Phylogeny; Arthritis, Infectious; Orthoreovirus, Avian; Canada; Viral Vaccines
PubMed: 36715479
DOI: 10.1637/aviandiseases-D-22-99997 -
Proceedings of the National Academy of... May 2023Mammalian orthoreoviruses (reoviruses) serve as potential triggers of celiac disease and have oncolytic properties, making these viruses potential cancer therapeutics....
Mammalian orthoreoviruses (reoviruses) serve as potential triggers of celiac disease and have oncolytic properties, making these viruses potential cancer therapeutics. Primary attachment of reovirus to host cells is mainly mediated by the trimeric viral protein, σ1, which engages cell-surface glycans, followed by high-affinity binding to junctional adhesion molecule-A (JAM-A). This multistep process is thought to be accompanied by major conformational changes in σ1, but direct evidence is lacking. By combining biophysical, molecular, and simulation approaches, we define how viral capsid protein mechanics influence virus-binding capacity and infectivity. Single-virus force spectroscopy experiments corroborated by in silico simulations show that GM2 increases the affinity of σ1 for JAM-A by providing a more stable contact interface. We demonstrate that conformational changes in σ1 that lead to an extended rigid conformation also significantly increase avidity for JAM-A. Although its associated lower flexibility impairs multivalent cell attachment, our findings suggest that diminished σ1 flexibility enhances infectivity, indicating that fine-tuning of σ1 conformational changes is required to successfully initiate infection. Understanding properties underlying the nanomechanics of viral attachment proteins offers perspectives in the development of antiviral drugs and improved oncolytic vectors.
Topics: Animals; Capsid Proteins; Reoviridae; Orthoreovirus; Viral Proteins; Virus Attachment; Antibodies, Viral; Mammals
PubMed: 37186838
DOI: 10.1073/pnas.2220741120 -
Viruses Feb 2021RNAs with methylated cap structures are present throughout multiple domains of life. Given that cap structures play a myriad of important roles beyond translation, such... (Review)
Review
RNAs with methylated cap structures are present throughout multiple domains of life. Given that cap structures play a myriad of important roles beyond translation, such as stability and immune recognition, it is not surprising that viruses have adopted RNA capping processes for their own benefit throughout co-evolution with their hosts. In fact, that RNAs are capped was first discovered in a member of the family, , before these findings were translated to other domains of life. This review revisits long-past knowledge and recent studies on RNA capping among members of to help elucidate the perplex processes of RNA capping and functions of RNA cap structures during infection. The review brings to light the many uncertainties that remain about the precise capping status, enzymes that facilitate specific steps of capping, and the functions of RNA caps during replication.
Topics: Animals; Humans; RNA Caps; RNA Processing, Post-Transcriptional; RNA, Viral; Reoviridae; Reoviridae Infections
PubMed: 33668598
DOI: 10.3390/v13020294 -
Virologie (Montrouge, France) Jun 2023As the world is experiencing the pandemic of SARS-CoV-2 responsible for COVID-19, one can wonder if members of other family of viruses could possibly emerge. Can such... (Review)
Review
As the world is experiencing the pandemic of SARS-CoV-2 responsible for COVID-19, one can wonder if members of other family of viruses could possibly emerge. Can such viruses establish a worldwide distribution with consequences similar to SARS-CoV-2? One such threat is the possible emergence of pathogenic reoviruses, especially by zoonotic transmission. Reoviruses are ubiquitous viruses exhibiting a worldwide distribution and various strains or isolates are found in many mammalian species and other vertebrates. When initially discovered, these viruses were named respiratory enteric orphan viruses (hence the acronym "reo") in order to reflect the fact that they could not be clearly associated with any given disease. However, this is not necessarily the case for all of these viruses, as clearly shown for some of these in animals. Significantly, there have been numerous reports of zoonotic transmission, especially from bats to humans. In this manuscript, pertinent properties of reoviruses will be first briefly presented followed by a review of available evidence for zoonotic transmission of pathogenic reoviruses to humans. Future work that appears to be needed for preparedness to the possible emergence of these viruses will then be briefly discussed.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Pandemics; Viruses; Orthoreovirus; Chiroptera
PubMed: 37462935
DOI: 10.1684/vir.2023.1008 -
Journal of Fish Diseases Sep 2020Piscine orthoreovirus infects various salmonid fish species, and the infection is associated with diseases such as heart and skeletal muscle inflammation (HSMI) in...
Piscine orthoreovirus infects various salmonid fish species, and the infection is associated with diseases such as heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar). There are no vaccines available or genetically selected resistant hosts that can efficiently control piscine orthoreovirus (PRV) infection. Currently, the only prophylactic measure against PRV is general biosecurity measures aiming to break the transmission cycle. Methods to eradicate infectious virus from contaminated facilities are desirable, but the knowledge on how to inactivate PRV is lacking. A major bottleneck for inactivation studies is the lack of ability to propagate PRV in cell culture. Therefore, in this study we developed an in vivo model for detection of infectious PRV particles after treatment of the virus with inactivation tools such as heat, pH, iodine, UV and commercially available disinfectants. The results show that standard iodine treatment is efficient in inactivation of the virus, and similarly are high and low pH extremes and treatment with Virocid, a commercially available disinfectant. A UV dose of at least 50 mJ/cm is required for inactivation, and the virus has high resistance against heat treatment.
Topics: Animals; Disinfectants; Fish Diseases; Hot Temperature; Hydrogen-Ion Concentration; Orthoreovirus; Reoviridae Infections; Salmo salar; Ultraviolet Rays
PubMed: 32632958
DOI: 10.1111/jfd.13214