JNK1 derived from orange-spotted grouper, Epinephelus coioides, involving in the evasion and infection of Singapore grouper iridovirus (SGIV)

c-Jun N-terminal kinase (JNK) regulates cellular responses to various extracellular stimuli, environmental stresses, pathogen infections, and apoptotic agents. Here, a JNK1, Ec-JNK1, was identified from orange-spotted grouper, Epinephelus coioides. Ec-JNK1 has been found involving in the immune response to pathogen challenges in vivo, and the infection of Singapore grouper iridovirus (SGIV) and SGIV-induced apoptosis in vitro. SGIV infection activated Ec-JNK1, of which phosphorylation of motif TPY is crucial for its activity. Over-expressing Ec-JNK1 phosphorylated transcription factors c-Jun and promoted the infection and replication of SGIV, while partial inhibition of the phosphorylation of Ec-JNK1 showed the opposite effects by over-expressing the dominant-negative EcJNK1-△183-185 mutant. Interestingly, SGIV enhanced the viral infectivity by activating Ec-JNK1 which in turn drastically inhibited the antiviral responses of type 1 IFN, indicating that Ec-JNK1 could be involved in blocking IFN signaling during SGIV infection. In addition, Ec-JNK1 enhanced the activation of AP-1, p53 and NF-κB, and resulted in increasing the levels of SGIV-induced cell death. The caspase 3-dependent activation correlated with the phosphorylation of Ec-JNK1 and contributed to SGIV-induced apoptosis. Taken together, SGIV modulated the phosphorylation of Ec-JNK1 to inactivate the antiviral signaling, enhance the SGIV-induced apoptosis and activate transcription factors for efficient infection and replication. The positive cooperativity molecular mechanism mediated by Ec-JNK1 contributes to the successful evasion and infection of iridovirus pathogenesis

Characterization of Coxsackievirus A6- and Enterovirus 71-associated Hand Foot and Mouth disease in Beijing, China, from 2013 to 2015

Background: Etiology surveillance of Hand Foot and Mouth disease (HFMD) in Beijing showed that Coxsackievirus A6 (CVA6) became the major pathogen of HFMD in 2013 and 2015. In order to understand the epidemiological characteristics and clinical manifestations of CVA6-associated HFMD, a comparison study among CVA6-, EV71- (Enterovirus 71) and CVA16- (Coxsackievirus A16) associated HFMD was performed.Methods: Epidemiological characteristics and clinical manifestations among CVA6-, EV71- and CVA16-associated mild or severe cases were compared from 2013 to 2015. VP1 gene of CVA6 and EV71 from mild cases, severe cases were sequenced, aligned and compared with strains from 2009 to 2015 in Beijing and strains available in GenBank. Phylogenetic tree was constructed by neighbor-joining method.Results: CVA6 became the predominant causative agent of HFMD and accounted for 35.4% and 36.9% of total positive cases in 2013 and 2015, respectively. From 2013 to 2015, a total of 305 severe cases and 7 fatal cases were reported. CVA6 and EV71 were responsible for 57.5% of the severe cases. Five out six samples from fatal cases were identified as EV71. High fever, onychomadesis and decrustation were the typical symptoms of CVA6-associated mild HFMD. CVA6-associated severe cases were characterized by high fever with shorter duration and twitch compared with EV71-associated severe cases which were characterized by poor mental condition, abnormal pupil and vomiting. Poor mental condition, lung wet rales, abnormal pupil and tachycardia were the most common clinical features of fatal cases. The percentage of lymphocyte in CVA6-associated cases was significantly lower than that of EV71. High percentage of lymphocyte and low percentage of neutrophils were the typical characteristics of fatal cases. VP1 sequences between CVA6- or EV71-associated mild and severe cases were highly homologous.Conclusion: CVA6 became one of the major pathogens of HFMD in 2013 and 2015 in Beijing. Epidemiological characteristics, clinical manifestations of CVA6-, EV71- and CVA16-associated cases in this study enriched the definition of HFMD caused by different pathogens and shed light to accurate diagnosis, appropriate treatment and effective prevention of HFMD