RT Journal Article SR Electronic(1) A1 Anzaghe, Martina A1 Kronhart, Stefanie A1 Niles, Marc A. A1 Höcker, Lena A1 Dominguez, Monica A1 Kochs, Georg A1 Waibler, ZoeYR 2021 T1 Type I interferon receptor-independent interferon-α induction upon infection with a variety of negative-strand RNA viruses JF Journal of General Virology, VO 102 IS 7 OP SP 001616 DO https://doi.org/10.1099/jgv.0.001616 PB Microbiology Society, SN 1465-2099, AB Type I interferons (IFNs) are a first line of defence against viral infections. Upon infection, a first small wave of early type I IFN, mainly IFN-β and particularly IFN-α4, are induced and bind to the type I IFN receptor (IFNAR) to amplify the IFN response. It was shown for several viruses that robust type I IFN responses require this positive feedback loop via the IFNAR. Recently, we showed that infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus lacking the ML open reading frame (THOV(ML-)) results in the expression of unexpected high amounts of type I IFN. To investigate if IFNAR-independent IFN responses are unique for THOV(ML-), we performed infection experiments with several negative-strand RNA viruses using different routes and dosages for infection. A variety of these viruses induced type I IFN responses IFNAR-independently when using the intraperitoneal (i.p.) route for infection. In vitro studies demonstrated that myeloid dendritic cells (mDC) are capable of producing IFNAR-independent IFN-α responses that are dependent on the expression of the adaptor protein mitochondrial antiviral-signalling protein (MAVS) whereas pDC where entirely depending on the IFNAR feedback loop in vitro. Thus, depending on dose and route of infection, the IFNAR feedback loop is not strictly necessary for robust type I IFN expression and an IFNAR-independent type I IFN production might be the rule rather than the exception for infections with numerous negative-strand RNA viruses., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001616