Respiratory syncytial virus tropism for olfactory sensory neurons in mice

• Published in: Journal of neurochemistry 2020-09, Vol.155 (2), p.137-153
• Main Authors: Bryche, Bertrand, Frétaud, Maxence, Saint‐Albin Deliot, Audrey, Galloux, Marie, Sedano, Laura, Langevin, Christelle, Descamps, Delphyne, Rameix‐Welti, Marie‐Anne, Eléouët, Jean‐François, Le Goffic, Ronan, Meunier, Nicolas
• Format: Article
• Language: English
• Subjects: Animal genetics; Animals; Axons; Bioluminescence; Blood-brain barrier; Central nervous system; Central Nervous System - diagnostic imaging; Central Nervous System - virology; Central Nervous System Diseases - diagnostic imaging; Central Nervous System Diseases - virology; Female; Genetics; Head - anatomy & histology; Imaging, Three-Dimensional; Immunohistochemistry; Life Sciences; Mice; Mice, Inbred BALB C; Microbiology and Parasitology; Molecular biology; Mucosa; nasal cavity; Nasal Mucosa - virology; Nervous system; Neuroimaging; Neurons; neurotropism; Nose; Odor; odorant binding protein; Odors; olfaction; Olfactory bulb; Olfactory Bulb - virology; Olfactory epithelium; Olfactory Mucosa - diagnostic imaging; Olfactory Mucosa - innervation; Olfactory Mucosa - virology; Olfactory receptor neurons; Olfactory Receptor Neurons - virology; Pathogens; Respiratory syncytial virus; Respiratory Syncytial Viruses; Respiratory tract; RNA, Viral - isolation & purification; Sensory evaluation; Sensory neurons; Smell; Steno's gland; Tissue analysis; Tissues; Toxicants; Tropism; Virology; Virus Replication; Viruses
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.14936

The olfactory mucosa, where the first step of odor detection occurs, is a privileged pathway for environmental toxicants and pathogens toward the central nervous system. Indeed, some pathogens can infect olfactory sensory neurons including their axons projecting to the olfactory bulb allowing them to bypass the blood–brain barrier and reach the central nervous system (CNS) through the so‐called olfactory pathway. The respiratory syncytial virus (RSV) is a major respiratory tract pathogen but there is growing evidence that RSV may lead to CNS impairments. However, the mechanisms involved in RSV entering into the CNS have been poorly described. In this study, we wanted to explore the capacity of RSV to reach the CNS via the olfactory pathway and to better characterize RSV cellular tropism in the nasal cavity. We first explored the distribution of RSV infectious sites in the nasal cavity by in vivo bioluminescence imaging and a tissue clearing protocol combined with deep‐tissue imaging and 3D image analyses. This whole tissue characterization was confirmed with immunohistochemistry and molecular biology approaches. Together, our results provide a novel 3D atlas of mouse nasal cavity anatomy and show that RSV can infect olfactory sensory neurons giving access to the central nervous system by entering the olfactory bulb. Cover Image for this issue: doi: 10.1111/jnc.14765. While the respiratory syncytium virus (RSV) is mainly known for its damaged in the respiratory tract, it could also impact the central nervous system. We explored globally the impact of RSV in the mouse nasal cavity and showed that RSV can infect olfactory sensory neurons giving access to the central nervous system by entering the olfactory bulb. Our study also provides a 3D atlas of the nasal cavity in mice giving tools to improve our understanding of virus tropism in the upper respiratory tract. Cover Image for this issue: 10.1111/jnc.14765.