Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43
- 31 August 2018
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 92 (17)
- https://doi.org/10.1128/JVI.00404-18
Abstract
Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences. IMPORTANCE Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.Funding Information
- CIHR Institute of infection and immunity (MT-9203)
This publication has 83 references indexed in Scilit:
- Simple piggyBac transposon-based mammalian cell expression system for inducible protein productionProceedings of the National Academy of Sciences of the United States of America, 2013
- Visualization of an Alphaherpesvirus Membrane Protein That Is Essential for Anterograde Axonal Spread of Infection in NeuronsmBio, 2012
- Glutamate Excitotoxicity Is Involved in the Induction of Paralysis in Mice after Infection by a Human Coronavirus with a Single Point Mutation in Its Spike ProteinJournal of Virology, 2011
- Murine Coronavirus Receptors Are Differentially Expressed in the Central Nervous System and Play Virus Strain-Dependent Roles in Neuronal SpreadJournal of Virology, 2010
- The Coronavirus Nucleocapsid Protein Is Dynamically Associated with the Replication-Transcription ComplexesJournal of Virology, 2010
- Effects of Coronavirus Infections in ChildrenEmerging Infectious Diseases, 2010
- Titration of Human Coronaviruses Using an Immunoperoxidase AssayJournal of Visualized Experiments, 2008
- Pathology and Pathogenesis of Severe Acute Respiratory SyndromeThe American Journal of Pathology, 2007
- α-Herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sitesThe Journal of cell biology, 2006
- Human coronavirus gene expression in the brains of multiple sclerosis patientsVirology, 1992