The overarching goal of our group is to understand the molecular mechanisms governing cytomegalovirus (CMV) replication, with a specific emphasis on understanding how CMVs establish, maintain and reactivate from latency in hematopoietic progenitor cells. In addition, we have contributed towards the development of CMV vaccine vectors both to make them safer as well as to understand the molecular basis for the unique and efficacious immune responses elicited by CMV vectors.

HCMV miRNAs and viral latency

HCMV encodes 14 miRNAs that we have shown play important roles both in lytic and latent infection by targeting components of cellular signaling pathways. A subset of the HCMV miRNAs are expressed in CD34+ hematopoietic progenitor cells (HPCs) and are critical for different stages of latency. We have several ongoing projects aimed at understanding the function(s) of these miRNAs in latency and reactivation.

HCMV proteins involved in viral latency

We collaborate with our colleagues at VGTI to investigate the interplay between viral miRNAs and viral proteins during lytic and latent infections in vitro and in vivo. In addition, we use our latency and reactivation model to study the role of other unique viral proteins.

RhCMV vaccine vectors

Our group works to understand the molecular requirements for RhCMV-based vaccine vectors to elicit HLA-E-restricted CD8+ T cells, which are necessary for protection against lethal SIV challenge. Intriguingly, viral miRNA-mediated alterations in endosomal trafficking appear to play an important role in HLA-E trafficking in the cell.