Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins

Cats are becoming more popular as household companions and pets, forming close relationships with humans. Although feline viral diseases can pose serious health hazards to pet cats, commercialized preventative vaccines are lacking. Interferons (IFNs), especially type I IFNs (IFN-α, IFN-β, and interferon omega (IFN-ω)), have been explored as effective therapeutic drugs against viral diseases in cats. Nevertheless, there is limited knowledge regarding feline IFN-ω (feIFN-ω), compared to IFN-α and IFN-β. In this study, we cloned the genes encoding feIFN-ωa and feIFN-ωb from cat spleen lymphocytes. Homology and phylogenetic tree analysis revealed that these two genes belonged to new subtypes of feIFN-ω. The recombinant feIFN-ωa and feIFN-ωb proteins were expressed in their soluble forms in Escherichia coli, followed by purification. Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin–Darby bovine kidney (MDBK), Madin–Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. The two novel feIFN-ω proteins (feIFN-ωa and feIFN-ωb) described in this study show promising potential to serve as effective therapeutic agents for treating viral infections in pet cats.

What do antagonists tell us about α-adrenoceptors?

The early proposals that pre- and post-junctional α-adrenoceptors might be different stemmed largely from two separate observations. Firstly, the orders of potency of a series of agonists at inhibiting the response to sympathetic nerve stimulation and in increasing inotropic activity in the rabbit isolated heart were different [1, 2]. Secondly, phenoxybenzamine was more potent in inhibiting vasoconstrictor responses to sympathetic nerve stimulation than in increasing transmitter overflow from the cat spleen [3]. These experiments illustrate the most fundamental, pharmacological ways of distinguishing between receptors: namely, by comparing the relative potencies of agonists and/or antagonists in producing, or preventing, pharmacological effects. There are, however, difficulties in using agonists to classify receptors because their ability to generate a response depends not only upon their intrinsic properties of affinity for, and efficacy at, the receptors but also upon the capacity of the tissue to translate the stimulus into a response. Thus agonists with a relatively low intrinsic efficacy may produce a small response, or no response at all, in a tissue in which the efficiency of the stimulus-response coupling mechanism is low. The importance of this phenomenon in influencing tissue responses to agonists with low efficacy has been demonstrated for the α-adrenoceptor agonist prenalterol [4] and for the α-adrenoceptor agonist oxymetazoline [5].