PKR-NF-κB Pathway Upstream of IFN-β Induction Is Dysregulated in Oncolytic Sindbis Virus-infected HeLa Cells

• Published in: Anticancer research Vol. 43; no. 7; pp. 2923 - 2932
• Main Authors: Ma, Xue, Ogawa, Tomoko, Tian, Zheng, Yi, Ruirong, Tang, Kang, Saito, Kengo, Yatabe, Sara, Ohno, Yoshifumi, Muroyama, Ryosuke, Ido, Eiji, Matsubara, Hisahiro, Shirasawa, Hiroshi
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.07.2023
• Subjects: Apoptosis; Caspase-3; eIF-2 kinase; eIF-2 Kinase - genetics; eIF-2 Kinase - metabolism; Fluorescence; Gene expression; HeLa Cells; Humans; Infections; Kinases; NF-kappa B - metabolism; NF-κB protein; Oncolysis; Protein kinase R; Protein Kinases; Proteins; RNA, Messenger - metabolism; Sindbis Virus; Upstream; Viruses; β-Interferon; NF-B; IFN-β; oncolytic; PKR; Sindbis virus
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.16463

Sindbis virus (SINV) is a naturally occurring oncolytic virus that kills cancer cells and is less harmful to normal cells. In this study, a recombinant SINV, which expressed green and blue fluorescent proteins, was used to precisely analyze SINV infection and replication. Antiviral responses, including IFN-β mRNA, protein kinase R (PKR), NF-B, and caspase 3/7, were analyzed in SINV-infected cancerous HeLa cells and normal human fibroblast TIG-1-20 cells. SINV could infect, replicate, and proliferate both in HeLa and TIG-1-20 cells, causing lytic infection only in HeLa cells. SINV grew preferentially in HeLa cells causing remarkable apoptosis. IFN-β mRNA expression was suppressed in SINV-infected HeLa cells compared to that in TIG-1-20 cells. Further analyses of PKR and NF-B upstream of IFN-β induction revealed that the compromised response in the PKR-NF-B pathway during early infection coincided with IFN induction suppression in HeLa cells. Dysregulation of PKR in HeLa cells is the determinant of SINV oncolysis.