1. DNA-PKcs restricts Zika virus spreading and is required for effective antiviral response
- Author
-
Patricio, Daniel De Oliveira, Dias, Greicy Brisa Malaquias, Granella, Lucilene Wildner, Trigg, Ben, Teague, Helena Claire, Bittencourt, Dina, Báfica, André, Zanotto-Filho, Alfeu, Ferguson, Brian, Mansur, Daniel Santos, and Apollo - University of Cambridge Repository
- Subjects
Zika Virus Infection ,Immunology ,Infant, Newborn ,interferon ,Zika Virus ,DNA ,Virus Replication ,Antiviral Agents ,infection ,Animals ,Humans ,Immunology and Allergy ,Interferons ,DNA-PKcs ,double-strand DNA breaks - Abstract
Peer reviewed: True, Zika virus (ZIKV) is a single-strand RNA mosquito-borne flavivirus with significant public health impact. ZIKV infection induces double-strand DNA breaks (DSBs) in human neural progenitor cells that may contribute to severe neuronal manifestations in newborns. The DNA-PK complex plays a critical role in repairing DSBs and in the innate immune response to infection. It is unknown, however, whether DNA-PK regulates ZIKV infection. Here we investigated the role of DNA-PKcs, the catalytic subunit of DNA-PK, during ZIKV infection. We demonstrate that DNA-PKcs restricts the spread of ZIKV infection in human epithelial cells. Increased ZIKV replication and spread in DNA-PKcs deficient cells is related to a notable decrease in transcription of type I and III interferons as well as IFIT1, IFIT2, and IL6. This was shown to be independent of IRF1, IRF3, or p65, canonical transcription factors necessary for activation of both type I and III interferon promoters. The mechanism of DNA-PKcs to restrict ZIKV infection is independent of DSB. Thus, these data suggest a non-canonical role for DNA-PK during Zika virus infection, acting downstream of IFNs transcription factors for an efficient antiviral immune response.
- Published
- 2022
- Full Text
- View/download PDF