Use of recombinant interferon omega in feline retrovirosis: From theory to practice

Abstract

Type-I interferons (IFNs) are cytokines that have non-specific antiviral activity, participating mostly in innate defense mechanisms. Their administration has been proposed to treat several viral and immunomediated diseases as an immunomodulatory therapy. Due to its availability, recombinant human interferon-alpha (rHuIFN-α) has been studied in relation to feline retrovirosis, both in vitro and in vivo. However, IFNs are species-specific and antibodies have been shown to develop in response to the high rHuIFN-α doses necessary for an effective therapy. A recombinant feline IFN has been developed, which has been characterized as interferon-omega (rFeIFN-ω), designed to overcome these problems. Nonetheless, very few studies have been undertaken to evaluate its efficacy in cats naturally infected with FIV or FeLV. In an initial study, we here demonstrated that rFeIFN-ω can dramatically improve the clinical condition of infected cats, and induce improvement of hematologic parameters. Minor changes or no change was observed for hypergammaglobulinemia, CD4/CD8 ratio, proviral load, viremia and RT activity, suggesting that the overall effect of IFN was on innate immunity. More studies are needed in order to better understand its in vivo mechanisms.

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

“…This activity indicates that cells have a tendency to be insensitive to IFN-ω from distantly related species [23]. IFN-ω is involved in the nonspecific response based on increased expression of several acute phase proteins and MHC I molecules; upregulation of the phagocytic activities of whole blood cells, macrophages and NK cell activities; and decreased concurrent viral excretion [71-74]. Different therapy protocols might also contribute to the distinct expression of innate immunity cytokines following IFN-ω treatment.…”

“…The first study supporting its clinical application was conducted in 2004 and found that cats infected with FeLV or co-infected FIV displayed a significant clinical improvement and a prolonged survival with rFeIFN-ω treatment [73, 116]. Other studies showed that treatment with rFeIFN-ω improved clinical signs, decreased concurrent viral excretion and hematologic parameters, and increased levels of acute phase proteins, a key component of the innate immune system [71, 119]. However, rFeIFN-ω did not change hypergammaglobulinemia, proviral load, or viremia.…”

Interferon-omega: Current status in clinical applications

“…Increasing evidence suggests that IFN-ω may be associated with the nonspecific immune response based on increased survival time, the presence of acute-phase proteins (serum amyloid-A, α-1-glycoprotein, and the C-reactive protein), the phagocytic activities of whole blood cells and macrophages, natural killer cell activities, and reduced concurrent viral excretion [44][45][46][47][48]. In general, increasing the number of ISGs, Mx proteins, and ZAPS, which could enhance pathogen detection and innate immune signaling, indicates that IFN-ω elicits an immune response.…”

Feline Immunodeficiency

“…AZT (3'-azido-2',3'-dideoxythymidine) is a nucleoside analogue (thymidine derivative) that blocks the retroviral reverse transcriptase and inhibits the replication of FIV in vivo and in vitro. As with HIV, FIV resistance may arise after 6 months of treatment Doménech et al, 2011;Mohammadi & Bienzle, 2012).…”