The host antiviral innate immune response involves activation of multiple signaling pathways that result in the production of type I interferons (IFN-I) and inflammatory cytokines, which together control virus infections. However, excessive inflammation and cytokine production can promote exacerbated disease. To achieve the right balance, these signaling pathways are regulated by different molecular processes, including the host ubiquitin system. This system is best known for its function in marking unnecessary proteins for degradation, but can also be used as a weapon against invading pathogens. However, viruses have developed mechanisms to hijack this system for its own use. For example, Zika virus hijacks a host antiviral factor, the E3-ubiquitin ligase TRIM7, which puts an ubiquitin marker on the viral envelope. This ubiquitin on the surface of the virus allows the virus to attach better to receptors expressed in specific cell types, driving the tissue specificity of Zika virus. Therefore, pathogenic viruses can hijack antiviral factors of the ubiquitin system, turning the antiviral functions of ubiquitin into ‘pro-viral’ pathogenic factors. This is a constant battle between the defensive response of the host cell and viruses, resulting in virus evolution and adaptation. In this talk, we will discuss novel molecular mechanism by which E3-ubiquitin ligases of the TRIM family regulate host antiviral pathways, and how different pathogenic viruses hijack the ubiquitin system to enhance virus replication.
1. Learn mechanisms of regulation of innate antiviral immune signaling that lead to protection against virus infection.
2. Strategies used by viruses to hijack host antiviral factors to enhance virus replication and pathology