The Cliffe Lab - University of Virginia School of Medicine

Cliffe Lab

Investigating the molecular mechanisms of Herpes Simplex Virus latency and reactivation, and neuronal specific immune responses.

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.

Research Interests

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 HSV manipulates the type of heterochromatin deposited to allow reactivation to occur 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.

Mission Statement

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 as a postdoc, postbac or research specialist please email Anna with a description of their research interests. Potential graduate students should apply through the UVA BIMS program.

Contact Us

Type I IFN dependent restriction of HSV latency

Latent HSV genomes have memory

Read our latest work from MSTP student Jon Suzich on how type I IFN upon de novo infection results in a more restricted form of HSV latency. We also link this restriction to association of viral genomes with PML nuclear bodies.

HSV reactivation in response to neuronal hyperexcitability and IL-1

Neuronal hyperexcitability is a DLK-dependent trigger of HSV-1 reactivation that can be induced by IL-1

The latest study from our lab published in eLife describes how HSV-1 reactivation can be induced by conditions that induce neuronal hyperexcitability including exposure IL-1. This study may help explain why HSV undergoes reactivation during fever, psychological stress and following sunburn.

HSV Phase I and phase II of reactivation

Neuronal Stress Pathway Mediates a Switch

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.

News All News »

May 2022

Graduate Student Sara Dochnal publishes her study on a novel in vitro model of HSV latency and demonstrates the requirement for DLK in "Phase I" viral gene expression. Check it…

May 2022

Our new study from graduate student Abigail Whitford on mechanisms of HSV reactivation from latently infected mice and role for host protein DLK published in Journal of Virology.

April 2022

Welcome new graduate student Patryk Krakowiak!

August 2021

Anna gave the Priscilla Schaffer Memorial Lecture at the Internal Herpesvirus Workshop. Read more about Priscilla and her numerous contributions to the herpesvirus field here.

July 2021

Alison and Sara wrote an incredibly comprehensive review on Polycomb targeting to herpesvirus genomes. This was just accepted for publication to Viruses.