Respiratory syncytial virus tropism for olfactory sensory neurons in mice

Bryche, Bertrand; Frétaud, Maxence; Deliot, Audrey Saint-Albin; Galloux, Marie; Sedano, Laura; Langevin, Christelle; Descamps, Delphyne; Rameix‐Welti, Marie‐Anne; Éléouët, Jean-François; Goffic, Ronan Le; Meunier, Nicolas

doi:10.1111/jnc.14936

Cited by 39 publications

(33 citation statements)

References 49 publications

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“…[24]. In mice, HRSV-infected cells were mainly found in the olfactory mucosa, which was recently observed by another group as well [30]. The olfactory mucosa contains olfactory receptor neurons, which are a potential route to the central nervous system [31].…”

Section: Discussionmentioning

confidence: 66%

In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus

Rijsbergen

Rennick

Laksono

et al. 2020

Journal of General Virology

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Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSVA11EGFP(5)]. A recombinant laboratory-adapted HRSV strain [rHRSVA2EGFP(5)] was used as a direct comparison. Our results show that rHRSVA11EGFP(5) replicated to higher viral titres than laboratory-adapted rHRSVA2EGFP(5) in the URT of cotton rats and mice. HRSV-infected cells were detected as early as 2 days post-inoculation in both species in the nasal septa and lungs. Infection was predominantly present in ciliated epithelial cells in cotton rats and in the olfactory mucosa of mice. In our opinion, this study highlights that the choice of virus strain is important when studying HRSV pathogenesis in vivo and demonstrates that A11 is a representative clinical-based virus. Additionally, we show critical differences in tropism and inflammation when comparing HRSV infection of cotton rats and mice.

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Section: Discussionmentioning

confidence: 66%

In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus

Rijsbergen

Rennick

Laksono

et al. 2020

Journal of General Virology

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“…Two recent reports indicate that olfactory neurons in hamster (Sia et al, 2020) and respiratory cells in ferret (Ryan et al, 2020) may be the target of SARS-CoV-2 but these studies did not focus on the nasal cavity and they did not use double staining to clearly identify the infected cells in the OE. We observed that SARS-CoV-2 can infect other nonneuronal cells in the nasal cavity, notably in the epithelium covering the lumen of Steno's gland which is however poorly described in the literature (Bryche et al, 2019b). Further studies are required to clearly identify the other non-neuronal cells infected by SARS-CoV-2 in the nasal cavity which may facilitate the systemic infection of other cell types and tissues lower in the respiratory airways.…”

Section: Discussionmentioning

confidence: 86%

“…We finally examined the presence of immune cells in the olfactory mucosa using Iba1+ as a specific marker of monocyte/macrophage lineage (Bryche et al, 2019b); (Fig. 4A).…”

Section: Infiltration Of Immune Cells In the Olfactory Epithelium Folmentioning

confidence: 99%

Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Bryche

Deliot

Murri

et al. 2020

Preprint

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145

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Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs.We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

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“…The axons of the olfactory neurons are a gate to the OB and provide a direct pathway to the CNS. Some viruses, like Influenza and Herpes simplex, exploit this olfactory pathway to access the OB, from which they can spread to other brain regions, as described in various animal models of infection [22].…”

Section: Discussionmentioning

confidence: 99%

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey

Spadera¹,

Viola

Pisani

et al. 2020

Eur Arch Otorhinolaryngol

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Purpose The presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity. Methods We developed a 15-item online questionnaire on "Sudden Olfactory Loss (SOL) and COVID-19" that was administered during March 2020 to Italian general practitioners registered to a social media group. Results One hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients. Conclusion SOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases. Level of evidence 4.

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Respiratory syncytial virus tropism for olfactory sensory neurons in mice

Cited by 39 publications

References 49 publications

In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus

In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus

Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey

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