The Cliffe Lab is part of the Department of Microbiology, Immunology and Cancer Biology (MIC) and the Neuroscience Graduate Program at the University of Virginia School of Medicine.
Our lab is interested in the mechanisms of Herpes Simplex Virus (HSV) latency and reactivation in neurons. HSV is a ubiquitous pathogen that infects approximately 67% of the world’s population. It hides for life in the form of a latent or silent infection of neurons and periodically reactivates, which can result in disease. The mechanisms regulating how the virus hides in neurons and how reactivation occurs are not understood. In addition, the long-term effects of HSV persistence on neuronal function are not known.
We use primary and differentiated neurons along with in vivo models to understand why HSV establishes a latent infection only in neurons and how the virus escapes from latency to reactivation. Our goals are to understand 1) how repressive chromatin is deposited on HSV genomes in neurons 2) how epigenetic modifications contribute to HSV latency 3) how gene silencing is reversed during reactivation, 4) how neurons sense and respond to HSV infection, and 5) the long-term impact of HSV infection on neuronal functions.
One questions we often get from people interested in joining the lab is what do we look for in a colleague? When looking for new members we value potential, enthusiasm and ability to work together as a team. We celebrate diversity, both in terms of race, gender, background, physical abilities and sexuality, and also intellectual diversity. We recognize that everyone has their strengths and areas that they struggle with, and we build on those strengths while working as a team to help everyone reach their full potential.
Therefore, anyone interested in working with us please email Anna with a description of their research interests.
A neuronal pathway involving activation of c-Jun N-terminal kinase (JNK), common to many stress responses, is essential for initial HSV gene expression during reactivation. JNK-dependent reactivation results in a specific change to the HSV epigenome known as a histone methyl/phospho switch, which can permit gene expression to occur from repressive heterochromatin. This study therefore answer a long-standing question as to how viral gene expression can initiate to trigger HSV reactivation.