Efecto in vitro de interferón de tipo I sobre la expresión de retrovirus felinos y evaluación de su aplicación terapéutica en gatos con infección natural

Abstract

Feline leukemia and feline immunodeficiency are two important diseases in small animal medicine. Currently, vaccination and control campaigns have significantly reduced their prevalence and incidence. However there is no cure any of these infections. Practitioners prescribe antiviral and/or immunomodulatory therapy to delay the disease progression, mainly, based on the positive results obtained with HIV. One of this immunomodulants is a human recombinant interferon (rHuIFN-α) registered to be used in HIV+ treatment. Easy oral application and low price are two advantages that make it a very interesting choice for both retroviral diseases. The present work evaluates the effect of IFN-α in cats naturally infected with feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The overall aim of this thesis was to analyze clinical and biopathological alterations and viral parameters and their evolution. This objective had the following three sub-objectives: 1. To analyse the in vitro effect of rHuIFN-α 2a, rHuIFN-α (A/D) and rFeIFN-ω on viral expression, reverse transcriptase activity (RT), viability, apoptosis, and viral RNA in feline lymphoid cell cultures infected with FeLV and FIV treated with these compounds. 2. To study the clinical, analytical and viral initial situation in a population of cats naturally infected with FeLV and FIV, to determine the alterations and significant correlations in both infections, and to have them as a reference value to develop sub-objective 3. 3. To evaluate the evolution of the clinical, analytical and viral infection in the group of cats orally treated with rHuIFN-α 2a (Roferon®). In vitro studies have shown that the synthesis of viral proteins (assessed by the expression of p27 in FeLV and p24 in FIV) did not decrease with the three interferons used, but they produced a statistically significant decrease in the number of infective viral particles (assessed by the presence of reverse transcriptase, RT). The decrease in the RT values depended on the time of exposure and the concentration of IFN. These results suggested that IFN reduced the formation of viral particles in cells infected with FeLV or FIV at a post translational viral replication point: maturation, assembly and/or release of viral particles. The experiments confirmed that the viability of infected cells decreased with treatment: in FeLV-infected cells it was due to the development of apoptosis, and in FIV-infected cells was due to necrosis. Therefore, interferon treatment reduced the release of viral particles due to the alteration of cellular membranes by apoptosis and necrosis, decreased viral load and the spread of infection to other cells ...