Kareem N. Mohni, Ph.D., is interested in virus-host interactions as they relate to human herpesviruses (HHVs). The nine HHVs are ubiquitous pathogens, with 90% of the U.S. population infected with three or more. HHVs are large, double-stranded DNA viruses that establish lifelong infections in those affected. DNA replication is an essential step of the virus life cycle and represents an appealing target for antiviral treatments.
The goal of Dr. Mohni's lab is to determine the host factors required for HHV DNA replication and restriction using novel proteomic and genetic approaches.
- Determine the role of host proteins in viral DNA replication. Herpesviruses rely on host proteins to replicate their DNA. Dr. Mohni and colleagues in his laboratory use quantitative proteomics to identify the host proteins associated with viral DNA combined with genetic and biochemical approaches to understand the mechanism of viral DNA replication.
- Manipulate the DNA damage response. Herpesviruses activate some DNA damage response pathways and inactivate others. Dr. Mohni's laboratory uses DNA double strand break repair assays, checkpoint signaling, quantitative proteomics and single molecule assays to study how HHVs manipulate the DNA damage response.
- Determine how host proteins restrict replication. Herpesvirus genomes are linear double-stranded DNA molecules that can elicit a cellular DNA damage response that would silence expression of viral genes. The viruses have evolved ways to suppress this response and promote replication. Dr. Mohni and colleagues seek to identify the host proteins that inhibit replication and promote latency.
Significance to patient care
HHVs cause lifelong infections and are the causative agents of many diseases including facial and genital ulcers, chickenpox, shingles, roseola, mononucleosis, and some cancers. HHVs often reactivate after immunosuppression, for example, after organ transplant or chemotherapy.
The only Food and Drug Administration-approved treatment for HHVs is acyclovir (and its derivatives). These drugs are effective, but the viruses quickly acquire resistance to them, especially in immunocompromised patients. The work in Dr. Mohni's laboratory will help identify new druggable targets in the herpesvirus life cycle.