Tumor suppressor p53 functions as an essential antiviral molecule against Japanese encephalitis virus

Japanese encephalitis virus （jEV） is a mosquito-borne virus of the family Flaviviridae. It is the causative agent of Japanese encephalitis with approximately 50,000 infection cases and 10,000 fatal cases annually in Asia （Erlanger et al., 2009）. Although liveattenuated JEV vaccine has been developed and used for human and pig vaccination, JE occurs epidemically or sporadically in some developing countries or even in vaccinated areas （Solomon, 2006）. Host resistance factors play an important role in the outcome of viral infection.

Molecular Characterization and Expression Analysis of SKIV Infection of Interferon-Induced Protein with Tetratricopeptide Repeats 1(IFIT1) in Epinephelus lanceolatus

Interferon-induced protein with tetratricopeptide repeats 1(IFIT1), also known as interferon-induced protein 56(IFI56) or Interferon-stimulated protein 56(ISG56), was originally identified as a protein induced upon treatment with interferon and inhibited by viral replication and translational initiation. In this study, Epinephelus lanceolatus IFIT1(ELIFIT1) gene was cloned for the first time. The complete cDNA of El IFIT1 gene includes 2921 nucleotides, and encodes a 437-amino acid(AA) protein. The putative ELIFIT1 protein has 9 TRP domains and is highly similar with IFIT1 proteins in other teleosts. In healthy fish, ELIFIT1 gene was highly expressed in the blood, which indicate its specific function in the peripheral immune system. Its expression was also observed in various immunity-related tissues including spleen, intestine, and kidney, Inducted with spotted knifejaw iridovirus(SKIV), ELIFIT1 gene expression was upregulated in the spleen, kidney, and liver 24 h after induction and reached its peak at 72 h, indicating that ELIFIT1 may play an important role in antivirus. These findings contribute to the understanding of the antiviral regulation of ELIFIT1 gene in teleost.

DAPK1(death associated protein kinase 1)mediates mTORC1 activation and antiviral activities in CD8^(+)T cells

Mechanistic target of rapamycin complex 1(mTORCt)regulates CD8^(+)T-cell differentiation and function.Despite the links between PI3K-AKT and mTORCI activation in CD8^(+)T cells,the molecular mechanism underlying mTORCI activation remains undear.Here,we show that both the kinase activity and the death domain of DAPK1 are required for maximal mTOR activation and CD8^(+)T-cell function.We found that TCR-induced activation of calcineurin activates DAPK1,which subsequently interacts with TSC2 via its death domain and phosphorylates TSC2 to mediate mTORCI activation.Furthermore,both the kinase domain and death domain of DAPK1 are required for CD8^(+)T-cell antiviral responses in an LCMV infection model.Together,our data reveal a novel mechanism of mTORCI activation that mediates optimal CD8^(+)T-cell function and antiviral activity.

The DEAD-Box RNA Helicase DDX1 Interacts with the Viral Protein 3D and Inhibits Foot-and-Mouth Disease Virus Replication

Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely elucidated.In the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV 3D.The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)cells.DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses.However,the roles of DDX1 during FMDV infection remain unclear.Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner.In addition,DDX1 stimulated IFN-p activation in FMDV-infected cells.Together,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.