ABSTRACT
Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in mammalian cells, is known to regulate the kinase-driven intracellular signaling pathways. Emerging evidences have shown that the PP2A phosphatase functions as a bona-fide therapeutic target for anticancer therapy, but it is unclear whether PP2A affects a porcine reproductive and respiratory syndrome virus infection. In the present study, we demonstrated for the first time that inhibition of PP2A activity by either inhibitor or small interfering RNA duplexes in target cells significantly reduced their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) infection. Further analysis revealed that inhibition of PP2A function resulted in augmented production of type I interferon (IFN). The mechanism is that inhibition of PP2A activity enhances the levels of phosphorylated interferon regulatory factor 3, which activates the transcription of IFN-stimulated genes. Moreover, inhibition of PP2A activity mainly blocked PRRSV replication in the early stage of viral life cycle, after virus entry but before virus release. Using type I IFN receptor 2 specific siRNA in combination with PP2A inhibitor, we confirmed that the effect of PP2A on viral replication within target cells was an interferon-dependent manner. Taken together, these findings demonstrate that PP2A serves as a negative regulator of host cells antiviral responses and provides a novel therapeutic target for virus infection.
Subject(s)
Host Microbial Interactions , Interferon Regulatory Factor-3/genetics , Interferon Type I/immunology , Porcine respiratory and reproductive syndrome virus/physiology , Protein Phosphatase 2/genetics , Virus Replication , Animals , Cells, Cultured , Interferon Regulatory Factor-3/immunology , Macrophages, Alveolar/virology , Okadaic Acid/pharmacology , Phosphorylation , Protein Phosphatase 2/antagonists & inhibitors , RNA, Small Interfering , Signal Transduction , SwineABSTRACT
To evaluate the neuroprotective effect of nerve growth factor ( NGF ) on acute angle-closure glaucoma patients after trabeculetomy.METHODS: Patients with viral keratitis who underwent trabeculectomy in treatment of acute angle - closure glaucoma in Xiamen Eye Center of Xiamen University from December 2011 to October 2013 were selected and completed the treatment, 61 eyes of 45 cases were followed up. The treatment group of 23 cases (32 eyes) with acute angle-closure glaucoma patients were treated by NGF gel for 3mo after trabeculetomy, while in the control group 22 cases (29 eyes) were treated by normal saline replaced NGF. All patients were followed up for at least 12mo, visual acuity, perimetry, retinal nerve fiber layer ( RNFL) thickness and cup/disc ratio of the patients were followed up during the treatment. The safety of topical use of NGF gel was also evaluated.RESULTS:ln all patients, the intraocular pressure ( lOP) was successfully controlled under 21mmHg and the visual acuity was markedly increased in the affected eye after trabeculectomy. Compared with control group, the postoperative lOP and visual acuity had no significant differences in treatment group (P>0. 05). The average light sensitivity of perimetry and mean defect were better than that in control group postoperative 6 and 12mo; The results of optical coherent tomography ( OCT ) and Heiderburg Retina Tomography ( HRT )-Ⅲ showed that RNFL thickness was significantly greater than that in control group, while cup/disc ratio significantly less than that in control group postoperative 6 and 12mo. Ocular surface damage, corneal endothelium to reduce and other eye complication were no observed in treatment group.CONCLUSlON:Acute angle-closure glaucoma treated by NGF gel after operation is effective and safe.
