Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / metabolism
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Antiviral Agents / pharmacology
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Camelids, New World* / immunology
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Camelids, New World* / metabolism
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Camelids, New World* / virology
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Chlorocebus aethiops
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Coronavirus Infections / immunology*
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Coronavirus Infections / metabolism
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Coronavirus Infections / prevention & control
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Coronavirus Infections / veterinary
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Disease Reservoirs / veterinary
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Disease Resistance / drug effects
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Disease Resistance / genetics
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Disease Resistance / immunology
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Gene Expression Regulation
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Immunity, Innate / physiology
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation / veterinary
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Inflammation / virology
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Interferon Lambda
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Interferon Type I / genetics
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Interferon Type I / metabolism*
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Interferon Type I / pharmacology
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Interferons / genetics
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Interferons / metabolism*
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Interferons / pharmacology
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Middle East Respiratory Syndrome Coronavirus / drug effects
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Middle East Respiratory Syndrome Coronavirus / immunology*
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Middle East Respiratory Syndrome Coronavirus / physiology
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Nasal Mucosa / drug effects
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Nasal Mucosa / immunology
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Nasal Mucosa / metabolism
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Nasal Mucosa / virology
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Respiratory System / drug effects
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Respiratory System / immunology
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Respiratory System / metabolism
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Respiratory System / virology
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Vero Cells
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Viral Load / drug effects
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Virus Replication / drug effects
Substances
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Antiviral Agents
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Interferon Type I
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Interferons
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Interferon Lambda
Grants and funding
This study was performed as part of the Veterinary Biocontained facility Network (VetBioNet) [EU Grant Agreement INFRA-2016-1 N°731014] and the Zoonotic Anticipation and Preparedness Initiative (ZAPI project) [Innovative Medicines initiative (IMI) grant 115760 to NT], with contributions from EFPIA partners, both supported by the European commission. IRTA is supported by CERCA Programme / Generalitat de Catalunya. NT is a recipient of a Chinese Scholarship Council grant (CSC NO. 201608150108). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.