ABSTRACT
Posttranscriptional modifications have been implicated in regulation of nearly all biological aspects of cellular RNAs, from stability, translation, splicing, nuclear export to localization. Chemical modifications also have been revealed for virus derived RNAs several decades before, along with the potential of their regulatory roles in virus infection. Due to the dynamic changes of RNA modifications during virus infection, illustrating the mechanisms of RNA epigenetic regulations remains a challenge. Nevertheless, many studies have indicated that these RNA epigenetic marks may directly regulate virus infection through antiviral innate immune responses. The present review summarizes the impacts of important epigenetic marks on viral RNAs, including N6-methyladenosine (m6A), 5-methylcytidine (m5C), 2'-O-methylation (2'-O-Methyl), and a few uncanonical nucleotides (A-to-I editing, pseudouridine), on antiviral innate immunity and relevant signaling pathways, while highlighting the significance of antiviral innate immune responses during virus infection.
ABSTRACT
OBJECTIVE: Though myasthenia gravis (MG) is a typical autoimmune disorder, there was some controversy on the treatment of the childhood-onset MG. By observing the efficacy of different therapies, the authors analyzed the affecting factors of prognosis in childhood-onset MG. METHOD: The retrospective data of 155 patients with childhood-onset MG (age of MG onset was less than 15 years) were collected from Department of Neurology, Beijing Tongren Hospital (January 2000 - February 2010). The patients were non-randomly divided according to their treatment into 3 groups (glucocorticoid, thymectomy and glucocorticoid combined with thymectomy groups). Postintervention status meeting the criteria of Myasthenia Gravis Foundation of America (MGFA) "complete stable remission, CSR", "pharmacologic remission, PR", "minimal manifestations, MM", or "Improved, I" was regarded as desirable response, which was used as primary indicator of observation. The authors assessed the efficacy of three therapies and analyzed the influencing factors of prognosis by using Chi-square test and Logistic regression. RESULT: At 3 months of treatment, glucocorticoid group showed the highest effective rate. At the end of 1 year or 2 years of treatment, glucocorticoid combined with thymectomy group showed the highest effective rate respectively. The generalization rate of MG at 2 years, 10 years and 20 years in childhood-onset ocular MG patients were 4.3%, 10.7%, and 41.5%, respectively. Of patients with generalization of MG, 48.1% occurred within 2 years, 92.6% within 20 years. Univariate analysis showed that in childhood-onset ocular MG patients, variables such as age at onset (> 10 years), LG-MG and with chronic fatigue were significantly associated with general MG conversion. Whereas multivariate analysis showed that patients with age at onset (> 10 years) and chronic muscle fatigue were apt to convert to generalized MG. CONCLUSION: Glucocorticoid appeared to have an effect that leads to early remission of symptoms in childhood-onset MG patients and glucocorticoid combined with thymectomy appeared to have better long-term effect. For those childhood-onset ocular MG patients with longer course of disease, older age of onset, chronic fatigue, or LG-MG, physicians should try to prevent the generalization of MG by immunosuppressive therapies.
