Cliffe Lab

Investigating Herpes Simplex Virus latency, epigenetics and host response

 

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 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.

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 please email Anna with a description of their research interests.

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.
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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.
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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.
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Connect with Cliffe Lab

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.

Twitter

Interested in *Key questions on the epigenetics of herpes simplex virus latency*? Check out our latest review in #PLOSPathogens from @AbigailWhitford.
https://dx.plos.org/10.1371/journal.ppat.1010587

Now for some good news - I can no longer call myself Assistant (to the) Professor.

Now Associate Professor Cliffe.

Next stop (🤞) tenure (because UVA does that separately)

Wow - really bad funding success for the lab. R01 from 33rd to 29th percentile. Previous R21 not sure the reviewers even read given the comments!

Well…we’re now out of funding.

Abortion is legal in Virginia.

Abortion will stay legal in Virginia so long as we remember that abortion rights are always on the ballot in Virginia.

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