What are the cellular consequences of viral DNA entry into the host cell nucleus?

The recent SARS-CoV-2 pandemic has underscored the need for detailed characterization of the mechanisms by which viruses infect and take over host cells. Cells have several mechanisms in place for recognizing and responding to viral infection, and several pathways are activated upon infection. In recent years, several viruses have been shown to specifically induce DNA damage responses (DDR), and in the cases of small DNA viruses, in particular, these responses can be exploited to establish viral replication compartments, redistribute host cellular replication machinery, arrest cell cycle progression and enhance the production of viral progeny. The mechanisms by which these processes take place are not fully understood. In some cases, these viruses directly cause damage to cellular DNA and in other cases, their replication ‘mimics’ damaged DNA. Cells have elaborate mechanisms in place to sense various kinds of damaged DNA, however, how the cells are ‘tricked’ by viruses into inducing damage responses is not clear.

Project Example: Characterization of viral degradation of host factors

One important aspect of viral pathogenesis is the degradation of host cell targets by virally encoded (or virally-modulated cellular) E3 ligases. Identifying these host cellular ‘enemies’ targeted by viruses can provide valuable insight into critical, protective cellular defense systems and can be helpful in controlling the course of viral infections. Several viral proteins have been known to interact with cellular E2s and E3s (for example, adenoviral E1A and E1B, polyomavirus T antigen, HPV E6 and E7, HIV Vif etc12.). Many of the host targets are important tumor suppressor genes including TP53, MRE11 and others. We will make use of our high-throughput degradation target discovery system to identify and characterize host targets upon viral infection.

Related publications

Adeyemi, Fuller et al, 2014
Adeyemi et al, 2012
Adeyemi et al, 2010