What is it about?
From the dromedary camel and all five living camelids, we have identified a novel type of mammalian interferon beta with four cysteine residues. Camelid IFN-β is unique with an even number of cysteines in the mature protein compared to other eutherian mammals with an odd number of cysteines .Recombinant camel beta interferon induced the expression of IFN-responsive genes and conferred antiviral resistance to camel kidney cells against camelpox virus. IFN-β from this unique group of mammals will offer insights into antiviral immune mechanisms and aid in the development of specific antivirals against pathogens that have the potential to be the next zoonotic pandemic.
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Why is it important?
Camelid IFN-β has an even number of cysteines in the mature protein, unlike other eutherian mammals with odd numbers . IFN-β from this unique group of mammals will help understand the antiviral immune mechanism and develop specific antivirals that protect against pathogens that could cause the next big pandemic.
Perspectives
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This page is a summary of: Beta interferons from the extant camelids: Unique among eutherian mammals, Developmental & Comparative Immunology, August 2022, Elsevier,
DOI: 10.1016/j.dci.2022.104443.
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Resources
Novel type-I interferons from the dromedary camel: Molecular identification, prokaryotic expression and functional characterization of camelid interferon-delta
The last two decades have seen the emergence of three highly pathogenic coronaviruses with zoonotic origins, which prompted immediate attention to the underlying cause and prevention of future outbreaks. Intensification of camel husbandry in the Middle East has resulted in increased human-camel interactions, which has led to the spread of potentially zoonotic viruses with human spillover risks like MERS-coronavirus, camelpox virus, etc. Type-I interferons function as the first line of defense against invading viruses and are pivotal for limiting viral replication and immune-mediated pathologies. Seven novel dromedary camel interferon delta genes were identified and cloned. Functional characterization of this novel class of IFNs from the mammalian suborder tylopoda is reported for the first time. The camel interferon-delta proteins resemble the reported mammalian counterparts in sequence similarity, conservation of cysteines, and phylogenetic proximity. Prokaryotically expressed recombinant camel interferon-δ1 induced IFN-stimulated gene expression and also exerted antiviral action against camelpox virus, an endemic zoonotic virus. The pre-treatment of camel kidney cells with recombinant camel IFN-δ1 increased cell survival and reduced camelpox virus in a dose-dependent manner. The identification of novel IFNs from species with zoonotic spillover risk such as camels, and evaluating their antiviral effects in-vitro will play a key role in improving immunotherapies against viruses and expanding the arsenal to combat emerging zoonotic pathogens.
Camelid type I interferons: Identification and functional characterization of interferon alpha from the dromedary camel (Camelus dromedarius)
Investigations into the molecular immune response of dromedary camel, a key livestock species of the arid, have been limited due to the lack of species-specific reagents. Here we describe for the first time, the identification and characterization of type I IFNs of dromedary camel, which are the most important cytokines in the innate host immune response against viruses. We cloned camel IFN-α coding sequences and identified a total of eleven subtypes. The canonical IFN-α subtype designated as IFN-α1 contained a 555-bp Open Reading Frame encoding a protein of 184 amino acids. Recombinant IFN-α1 protein was produced in E. coli and purified from inclusion bodies. Recombinant camel IFN-α1 induced the mRNA expression of interferon-stimulated genes (ISGs) in camel kidney cells. The purified protein also showed potent in-vitro antiviral activity against Camelpox Virus in kidney cells. The identified camel IFN-α protein and the subtypes will facilitate a better understanding of the host immune response to viral infections in camel and the development of potential antiviral biologicals for zoonotic diseases for which camel act as a reservoir.
Camelid IFNs could play important role in combating emerging zoonotic pathogens
Within the last two decades, the emergence and global impact of three highly pathogenic coronaviruses of zoonotic origin have compelled rapid attention to anthropogenic drivers of disease evolution and the prevention of potential future zoonotic outbreaks. Numerous zoonotic viruses could lead to the next pandemic after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Camelids are the sole survivors of the mammalian suborder Tylopoda, which first appeared 40 million years ago. The Camelidae are a family of superbly adapted animals that live in particular ecological niches with harsh temperatures, little foliage, food, and water. Camelini (Old World Camels) is comprised of only one genus and two species. Llama (Lama glama), Guanaco (Lama guanicoe), Vicugna (Vicugna vicugna), and Alpaca (Alpaca vicugna) are the four species of the Lamini (New World camelids). The Camelidae family has a remarkable level of conservation, with all extant individuals having the same chromosome number and possessing distinct heavy-chain antibodies. In a recent study published in the Developmental & Comparative Immunology journal, the discovery of a novel form of mammalian interferon-Beta (IFN-β) with four cysteine residues from the dromedary camel and the five remaining members of the mammalian suborder Tylopoda is described. Following infection with the camelpox virus and stimulation with the viral mimic poly, the expression of IFN-β mRNA was examined. In vitro, recombinant dromedary IFN-β generated in a prokaryotic expression system increased the expression of IFN-responsive genes in camel kidney cells and provided antiviral resistance to camelpox virus. Camelid IFNs are anticipated to be important in the fight against new zoonotic diseases found in camelids.
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