Efficacy of HIV-1 Clade B Tat Protein Treatment of Experimental Autoimmune Neuritis in Rats

Abstract

This research was focused to investigate the use of Tat clade B for HIV-1 to treat Guillain-Barre Syndrome (GBS). This investigation was conducted with a Lewis rat model to induce experimental autoimmune neuritis (EAN) as the disease model for GBS. The first aim of this research proposal was to determine the distance and velocity of EAN in Lewis rats with the treatment of clade B Tat proteins. The second aim was to determine if EAN can be reduced with clade B Tat proteins in Lewis rats by analyzing the level of neuropathy with Iba-1 and GFAP immunofluorescence analysis, which are overexpressed in EAN models. The third aim was to determine if clade B Tat protein can reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines in Lewis rats with EAN. The pro-inflammatory cytokines analyzed were IFN-γ, TNF-α, IL-6, and IL-17A. The anti-inflammatory cytokines were IL-4 and IL-10. The fourth aim was to determine if HIV-1 clade B Tat protein can influence the proportions of CD4+ T-cells, cytotoxic T-cells and Treg cells in Lewis rats with EAN. The fifth aim was to determine if HIV-1 clade B Tat protein can reduce recruitment of inflammatory cells and myelin sheath degradation with Lewis rats with EAN. The sixth aim was to determine presence of P2 antibody concentrations amongst test groups. This study showed that treatment with Tat protein improved rotarod performance for only the diseased female group, but no improvement in performance on the open field tests for either sex test group. This study also showed that treatment of Tat helped with reducing certain pro-inflammatory cytokines and increasing IL-4. Iba-1 and GFAP expression was higher in EAN test groups treated with clade B Tat protein for female Lewis rats, but reduced expression in male group treated with higher doses of clade B Tat protein. Cytotoxic T-cells were found to decrease and Treg cells increased suggesting that Tat protein treatment helps with reducing the autoimmune attack on the peripheral nervous system. Hematoxylin and eosin (H&E) and luxol fast blue stains showed less inflammatory cells and myelin sheath degradation with Tat treatment. P2 antibodies were present for induced EAN rats and reduced with Tat treatment for both sexes.