Induction of a systemic antiviral state in vivo in the domestic cat with a class A CpG oligonucleotide

The evolution of cats as a solitary species has pressured feline viruses to develop highly efficient transmission strategies, the ability to persist within the host for long periods of time and the aptitude to adapt to natural and vaccine-induced immunological pressures. These characteristics render feline viruses particularly dangerous in catteries, shelters and rescue homes, were cats from different backgrounds live in close proximity. The possibility to induce short-term resistance of newcomer cats to a broad variety of viruses could help prevent the dissemination of viruses both within and outside such facilities. Oligonucleotides (ODN) containing unmethylated cytosine phosphate guanosine (CpG) motifs stimulate innate immune responses in mammals. We have previously shown that ODN 2216, a class A CpG ODN, promotes the expression by feline immune cells of potent antiviral molecules that increase resistance of feline fibroblastic and epithelial cell lines to five common feline viruses. With the aim to test the safety and extent of the biological effects of ODN 2216 in the domestic cat, we performed an initial in vivo experiment in which two cats were injected the molecule once subcutaneously and two additional cats received control treatments. No side effects to administration of ODN 2216 were observed. Moreover, this molecule induced the expression of the myxovirus resistance (Mx) gene, a marker for the instigation of innate antiviral processes, in blood as well as in oral, conjunctival and rectal mucosa cells, indicating systemic biological activity of the molecule with protective potential at viral entry sites. Mx mRNA levels were already elevated in blood 6 h post injection of ODN 2216, reached peak levels within 24 h and returned to basal values by 96–192 h after administration of the molecule. Similar induction patterns were observed in all analyzed mucosal cells. Plasma collected from treated cats at regular intervals until 96–192 h could moreover induce Mx mRNA expression in fcwf-4 cells and increase resistance of these cells to feline calicivirus inoculation. Finally, Mx mRNA levels measured in blood correlated with the degree of viral inhibition that was induced by plasma from the same cat and the same experimental time point. Our results altogether underline the promising potential of ODN 2216 in promoting antiviral defense mechanisms and inducing temporary resistance to viral infections in vivo in the domestic cat.