Publication Date:
2018
Description:
〈p〉The auxiliary β〈sub〉4〈/sub〉 subunit of the cardiac Ca〈sub〉v〈/sub〉1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β〈sub〉4〈/sub〉 subunit in H9c2 rat cardiac cells on the abundances of 〈i〉Ifnb〈/i〉 mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β–related genes 〈i〉Ddx58〈/i〉, 〈i〉Ifitm3〈/i〉, 〈i〉Irf7〈/i〉, 〈i〉Stat2〈/i〉, 〈i〉Ifih1〈/i〉, and 〈i〉Mx1〈/i〉, as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the β〈sub〉4〈/sub〉 subunit in H9c2 cells reduced the expression of IFN-β–stimulated genes. In response to inhibition of the kinase JAK1, the abundances of β〈sub〉4〈/sub〉 subunit mRNA and protein were decreased. β〈sub〉4〈/sub〉 subunit abundance was increased, and it translocated to the nucleus, in cells treated with IFN-β, infected with dengue virus (DENV), or transfected with poly(I:C), a synthetic analog of double-stranded RNA. Cells that surrounded the virus-infected cells showed translocation of β〈sub〉4〈/sub〉 subunit proteins to nuclei in response to spreading infection. We showed that the β〈sub〉4〈/sub〉 subunit interacted with the transcriptional regulator IRF7 and that the activity of an 〈i〉Irf7〈/i〉 promoter–driven reporter was increased in cells overexpressing the β〈sub〉4〈/sub〉 subunit. Last, overexpressing β〈sub〉4〈/sub〉 in undifferentiated and differentiated H9c2 cells reduced DENV infection and decreased the abundance of the viral proteins NS1, NS3, and E-protein. DENV infection and poly(I:C) also increased the concentration of intracellular Ca〈sup〉2+〈/sup〉 in these cells. These findings suggest that the β〈sub〉4〈/sub〉 subunit plays a role in promoting the expression of IFN-related genes, thereby reducing viral infection.〈/p〉
Print ISSN:
1945-0877
Electronic ISSN:
1937-9145
Topics:
Biology
,
Medicine
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