The β4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells

Eshwar R. Tammineni, Elba D. Carrillo, Rubén Soto-Acosta, Antonio H. Angel-Ambrocio, María C. García, Patricia Bautista-Carbajal, Rosa M. Del Angel, Jorge A. Sánchez

Research output: Contribution to journalArticle

Abstract

The auxiliary β4 subunit of the cardiac Cav1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β-related genes Ddx58, Ifitm3, Irf7, Stat2, Ifih1, and Mx1, as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the β4 subunit in H9c2 cells reduced the expression of IFN-β-stimulated genes. In response to inhibition of the kinase JAK1, the abundances of β4 subunit mRNA and protein were decreased. β4 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 β4 subunit proteins to nuclei in response to spreading infection. We showed that the β4 subunit interacted with the transcriptional regulator IRF7 and that the activity of an Irf7 promoter-driven reporter was increased in cells overexpressing the β4 subunit. Last, overexpressing β4 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 Ca2+ in these cells. These findings suggest that the β4 subunit plays a role in promoting the expression of IFN-related genes, thereby reducing viral infection.

Original languageEnglish (US)
Article numbereaaj1676
JournalScience Signaling
Volume11
Issue number560
DOIs
StatePublished - Dec 11 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The β<sub>4</sub> subunit of Ca<sub>v</sub>1.2 channels is required for an optimal interferon response in cardiac muscle cells'. Together they form a unique fingerprint.

  • Cite this

    Tammineni, E. R., Carrillo, E. D., Soto-Acosta, R., Angel-Ambrocio, A. H., García, M. C., Bautista-Carbajal, P., Del Angel, R. M., & Sánchez, J. A. (2018). The β4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells. Science Signaling, 11(560), [eaaj1676]. https://doi.org/10.1126/scisignal.aaj1676