Defective Viral Genomes: Critical Danger Signals of Viral Infections

Current and proposed models of the events required for the development of effective antiviral responses to infections with paramyxoviruses. (A) According to current paradigms, viral recognition is maximized by type I IFN signaling that promotes the expression of essential viral sensors and signaling molecules. This paradigm assumes a low level of expression of type I IFN. In the depicted example of SeV infection, this scenario is possible if the virus-encoded V and C antagonistic proteins are only partially active, for example, during a zoonotic infection. However, this scenario cannot explain the induction of the antiviral response in the natural host of this virus, which is effectively blocked by the viral antagonists. (B) The model developed by my laboratory proposes that defective viral genomes that arise at high levels of virus replication provide potent danger signals that stimulate the host antiviral response to overcome viral antagonism, independently of type I IFN feedback.