Manipulation of Non-canonical NF-κB Signaling by Non-oncogenic Viruses

Nuclear factor (NF)-κB is a major regulator of antiviral response. Viral pathogens exploit NF-κB activation pathways to avoid cellular mechanisms that eliminate the infection. Canonical (classical) NF-κB signaling, which regulates innate immune response, cell survival and inflammation, is often manipulated by viral pathogens that can counteract antiviral response. Oncogenic viruses can modulate not only canonical, but also non-canonical (alternative) NF-κB activation pathways. The non-canonical NF-κB signaling is responsible for adaptive immunity and plays a role in lymphoid organogenesis, B cell development, as well as bone metabolism. Thus, non-canonical NF-κB activation has been linked to lymphoid malignancies. However, some data strongly suggest that the non-canonical NF-κB activation pathway may also function in innate immunity and is modulated by certain non-oncogenic viruses. Collectively, these findings show the importance of studying the impact of different groups of viral pathogens on alternative NF-κB activation. This mini-review focuses on the influence of non-oncogenic viruses on the components of non-canonical NF-κB signaling.