Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are features of alpacas resolving MERS-CoV infection.
Animals
Antiviral Agents
/ metabolism
Camelids, New World
/ immunology
Chlorocebus aethiops
Coronavirus Infections
/ immunology
Disease Reservoirs
/ veterinary
Disease Resistance
/ drug effects
Gene Expression Regulation
Immunity, Innate
/ physiology
Inflammation
/ immunology
Interferon Type I
/ genetics
Interferons
/ genetics
Middle East Respiratory Syndrome Coronavirus
/ drug effects
Nasal Mucosa
/ drug effects
Respiratory System
/ drug effects
Vero Cells
Viral Load
/ drug effects
Virus Replication
/ drug effects
Interferon Lambda
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
17
12
2020
accepted:
19
04
2021
revised:
11
06
2021
pubmed:
25
5
2021
medline:
24
6
2021
entrez:
24
5
2021
Statut:
epublish
Résumé
While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, while interferon stimulated genes (ISGs) were induced along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, seems central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.
Identifiants
pubmed: 34029358
doi: 10.1371/journal.ppat.1009229
pii: PPATHOGENS-D-20-02713
pmc: PMC8195365
doi:
Substances chimiques
Antiviral Agents
0
Interferon Type I
0
Interferons
9008-11-1
Interferon Lambda
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009229Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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