Human cytomegalovirus (HCMV) is a herpesvirus that persists in 60-99% of the population through a latent infection that results in significant morbidity and mortality following reactivation in individuals with weakened immunity. Latent coexistence is one of the least understood phenomena in virology, but critically important to understanding viral pathogenesis and the impact of viral coexistence on our biology. My research program focuses on identifying the molecular interactions between the virus and the host cell using primary human hematopoietic progenitor cells (HPCs) that culminate in latency. To this end, I have developed a novel in vitro model for HCMV latency and identified the first virus-coded determinant required for latency. We are also exploring the role of cellular mechanisms and pathways that are important to latency. These include the innate immune response to infection and epigenetic regulation of gene expression. Further, we are developing an in vivo model to analyze the impact of latent and productive infection on HPC biology. Identifying virus-host interactions unique to the latent infection will elucidate the mechanisms required for latency and, consequently, those impacting viral pathogenesis.
As an Innovation Fund investigator, Goodrum’s lab is teaming with the lab of Benjamin R. tenOever, Ph.D., to look for ways to better understand how viruses cause infections. This grant allows them to combine efforts in developing a system to study HCMV in cell types important to viral persistence. Goodrum and tenOever will devise a system to better manipulate the virus to determine the function of specific viral genes. Their findings are poised to advance understanding of how viruses lie dormant to cause persistent infections, and may ultimately result in new ways of controlling virus replication and developing an effective HCMV vaccine.