The emergence of the novel ß-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19). Clinical studies have documented that potentially severe neurological symptoms are associated with SARS-CoV-2 infection, thereby suggesting direct CNS penetration by the virus. Prior studies have demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). By comparison, it has been hypothesized that a similar mechanism exists to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS. Genetic engineering of the RABV has been employed to generate novel vaccines consisting of non-replicating RABV particles expressing chimeric capsid proteins containing human immunodeficiency virus 1 (HIV-1), Middle East respiratory syndrome (MERS-CoV), Ebolavirus, and hepatitis C virus (HCV) sequences. Accordingly, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex.
- MeSH
- Betacoronavirus chemie imunologie MeSH
- glykoprotein S, koronavirus chemie genetika imunologie MeSH
- koronavirové infekce imunologie metabolismus prevence a kontrola virologie MeSH
- lidé MeSH
- nikotinové receptory metabolismus MeSH
- pandemie MeSH
- proteinové domény MeSH
- replikace viru * MeSH
- virová pneumonie imunologie virologie MeSH
- virové vakcíny chemie imunologie metabolismus MeSH
- virus rabies genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.
- MeSH
- Bayesova věta MeSH
- biologická evoluce * MeSH
- Chiroptera virologie MeSH
- genom virový MeSH
- interakce hostitele a patogenu * MeSH
- mikrosatelitní repetice genetika MeSH
- rabies epidemiologie MeSH
- roční období MeSH
- typy dědičnosti genetika MeSH
- virus rabies genetika MeSH
- zeměpis MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Geografické názvy
- Peru epidemiologie MeSH
Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.
- MeSH
- atenuované vakcíny * MeSH
- divoká zvířata * MeSH
- genetická variace MeSH
- genom virový MeSH
- nemoci zvířat prevence a kontrola MeSH
- rabies veterinární MeSH
- RNA virová MeSH
- vakcína proti vzteklině genetika imunologie MeSH
- vakcinace veterinární MeSH
- virus rabies genetika imunologie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
