RESUMEN
The Pro-Ser-Ala-Pro (PSAP) motif in the p2 domain of feline immunodeficiency virus (FIV) Gag is required for efficient virus release, virus replication, and Gag binding to the ubiquitin-E2-variant (UEV) domain of Tsg101. As a result of this direct interaction, expression of an N-terminal fragment of Tsg101 containing the UEV domain (referred to as TSG-5') inhibits FIV release. In these respects, the FIV p2(Gag) PSAP motif is analogous to the PTAP motif of HIV-1 p6(Gag). To evaluate the feasibility of a late domain-targeted inhibition of virus replication, we created an enriched Crandell-Rees feline kidney (CRFK) cell line (T5'(hi)) that stably expresses high levels of TSG-5'. Here we show that mutations in either the V3 loop or the second heptad repeat (HR2) domain of the FIV envelope glycoprotein (Env) rescue FIV replication in T5'(hi) cells without increasing FIV release efficiency. TSG-5'-resistance mutations in Env enhance virion infectivity and the cell-cell spread of FIV when diffusion is limited using a semi-solid growth medium. These findings show that mutations in functional domains of Env confer TSG-5'-resistance, which we propose enhances specific infectivity and the cell-cell transmission of virus to counteract inefficient virus release. This article is part of a Special Issue entitled: Viral Membrane Proteins-Channels for Cellular Networking.
Asunto(s)
Proteínas de Unión al ADN/fisiología , Complejos de Clasificación Endosomal Requeridos para el Transporte/fisiología , Virus de la Inmunodeficiencia Felina/patogenicidad , Mutación , Fragmentos de Péptidos/fisiología , Factores de Transcripción/fisiología , Proteínas del Envoltorio Viral/fisiología , Animales , Gatos , Células Cultivadas , Mutagénesis Sitio-DirigidaRESUMEN
Aloe emodin is isolated compound of aloe vera which is used traditionally as an anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl or sulfated forms of aloe emodin may provide some limitations in its absorption capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO) and prostaglandin E2, via its action on murine macrophages. However, present work evidenced that molecular docking of aloe emodin modulates the anti-inflammatory activity, as well as expression of COX-2 (cyclooxygenase-2) in rodent. The AEC (4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2 carboxylic acid) was synthesized using aloe emodin as starting material. The study was planned for evaluation of possible anti-inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and complete Freund's adjuvant induced arthritis in rats. The AE (aloe emodin) and AEC significantly (P < 0.001) reduced carrageenan induced paw edema at 50 and 75 mg/kg. Complete Freund's adjuvant induced arthritis model showed significant (P < 0.001) decrease in injected and noninjected paw volume, arthritic score. AE and AEC showed significant effect on various biochemical, antioxidant, and hematological parameters. Diclofenac sodium 10 mg/kg showed significant (P < 0.001) inhibition in inflammation and arthritis.