摘要：SummaryType 1 interferon (IFN) plays a critical role in early antiviral defense and priming of adaptive immunity by signaling upregulation of host antiviral IFN-stimulated genes (ISGs). Certain stimuli trigger strong activation of IFN regulatory factor 3 (IRF3) and direct upregulation of ISGs in addition to IFN. It remains unclear why some stimuli are stronger activators of IRF3 and how this leads to IFN-independent antiviral protection. We found that UV-inactivated human cytomegalovirus (HCMV) particles triggered an IFN-independent ISG signature that was absent in cells infected with UV-inactivated Sendai virus particles. HCMV particles triggered mostly uniform activation of IRF3 and low-level IFN-βproduction within the population while SeV particles triggered a small fraction of cells producing abundant IFN-β. These findings suggest that population-level activation of IRF3 and antiviral protection emerges from a diversity of responses occurring simultaneously in single cells. Moreover, this occurs in the absence of virus replication.Graphical AbstractDisplay OmittedHighlights•The antiviral response to virus particles requires low levels of interferon•Cells respond differently to HCMV or SeV particles•Heterogeneous IRF3 activation influences the response to virusBiological Sciences; Molecular Biology; Microbiology; Virology; Cell Biology
