Anna Cliffe

Associate Professor, Microbiology, Immunology, and Cancer Biology

Primary Location

Pinn, Rm 7034
Charlottesville, Virginia

Primary Phone Number

434.924.7779

Fax Number

434.982.1071

[email protected]

Website

https://med.virginia.edu/research/microbiology-immunology-cancer-biology/labs/cliffe

Bio & Overview

Research description: Herpes simplex viruses type 1 and type 2 are significant human pathogens. Approximately 65% of the US population are infected with HSV-1 and 20% with HSV-2. The viruses persist in the body for life in the form of a latent, or silent, infection of neurons. Periodically, the viruses reactivate from latency to allow transmission to a new host, which can be associated with disease including cold sores, kerato-conjunctivitis, genital lesions and encephalitis. The Cliffe lab investigates the mechanisms of herpes simplex virus (HSV) latency and reactivation in neurons. We use primary and differentiated neurons along with in vivo models to determine how HSV establishes a latent infection in neurons and how the virus reactivates under conditions of cell stress. Our goals are to understand the following: 1) Why does HSV latency occurs ONLY in neurons? We are investigating the unique properties of neurons that allows HSV to establish a latent infection. Examples of projects include investigating how infection through axons is more repressive than infection through the soma and links between increased resistance to cell death in neurons and enhanced anti-viral responses. 2) How does HSV gene silencing occurs in neurons? During latency, the HSV genome associates with silent, heterochromatin. However, the mechanisms by which heterochromatin is targeted to the viral genome and the proteins associated with the genome are not known. We are investigating how heterochromatin forms on the HSV genome following neuronal infection and the exact nature of the viral chromatin. We are also interested in how differences in the chromatin structure of the latent HSV-1 and HSV-2 genomes influence the ability of the viruses to reactivate. 3) How does the HSV genome become de-repressed during reactivation? In order for HSV to reactivate, the silent heterochromatin on the viral genome needs to be remodeled to allow gene expression to occur. We are investigating links between activation of cell stress pathways in neurons and remodeling of the viral chromatin during reactivation. By understanding how the viral chromatin needs to be remodeled we hope to develop therapies that act on the viral chromatin and prevent reactivation occurring.

Academic Information

Department: Microbiology, Immunology, and Cancer Biology

Academic Title: Assistant Professor

Primary Education

PhD, Edinburgh University, Edinburgh, Scotland, UKnull

Other Appointments

Assistant Professor, Neuroscience

Other Affiliations

MSTP
BIMS

Research Interests

Herpes Simplex Virus Infection of Neurons

Research Disciplines

Epigenetics
Immunology
Infectious Diseases/Biodefense
Microbiology
Molecular Biology
Neuroimmunology
Neuroscience

Research Opportunities

Epigenetics
Infectious Diseases
Microbiology
Molecular Biology
Neuroimmunology

PhD Programs

Microbiology
Neuroscience

Selected Publications

2024

Cuddy, S. R., Flores, M. E., Krakowiak, P. A., Whitford, A. L., Dochnal, S. A., Babnis, A., . . . Cliffe, A. R. (2024). Co-option of mitochondrial nucleic acid sensing pathways by HSV-1 UL12.5 for reactivation from latent Infection.. bioRxiv. doi:10.1101/2024.07.06.601241

Francois, A. K., Rohani, A., Loftus, M., Dochnal, S., Hrit, J., Mcfarlane, S., . . . Cliffe, A. R. (2024). Single-genome analysis reveals a heterogeneous association of the herpes simplex virus genome with H3K27me2 and the reader PHF20L1 following infection of human fibroblasts. MBIO, 15(4). doi:10.1128/mbio.03278-23

Rasmussen, A. L., Gronvall, G. K., Lowen, A. C., Goodrum, F., Alwine, J., Andersen, K. G., . . . Yurochko, A. (2024). Virology-the path forward (vol 98, e0179123, 2024). JOURNAL OF VIROLOGY, 98(3). doi:10.1128/jvi.00074-24

Dochnal, S. A., Whitford, A. L., Francois, A. K., Krakowiak, P. A., Cuddy, S., & Cliffe, A. R. (2024). c-Jun signaling during initial HSV-1 infection modulates latency to enhance later reactivation in addition to directly promoting the progression to full reactivation. JOURNAL OF VIROLOGY. doi:10.1128/jvi.01764-23

Rasmussen, A. L., Gronvall, G. K., Lowen, A. C., Goodrum, F., Alwine, J., Andersen, K. G., . . . Yurochko, A. (2024). Virology-the path forward. JOURNAL OF VIROLOGY, 98(1). doi:10.1128/jvi.01791-23

2023

Francois, A. K., Rohani, A., Loftus, M., Dochnal, S., Hrit, J., McFarlane, S., . . . Cliffe, A. R. (2023). Single-genome analysis reveals heterogeneous association of the Herpes Simplex Virus genome with H3K27me2 and the reader PHF20L1 following infection of human fibroblasts.. bioRxiv. doi:10.1101/2023.12.03.569766

Dochnal, S. A., Whitford, A. L., Francois, A. K., Krakowiak, P. A., Cuddy, S., & Cliffe, A. R. (2023). c-Jun Signaling During Initial HSV-1 Infection Modulates Latency to Enhance Later Reactivation in addition to Directly Promoting the Progression to Full Reactivation.. bioRxiv. doi:10.1101/2023.11.10.566462

Cuddy, S. R., & Cliffe, A. R. (2023). The Intersection of Innate Immune Pathways with the Latent Herpes Simplex Virus Genome. JOURNAL OF VIROLOGY, 97(5). doi:10.1128/jvi.01352-22

Goodrum, F., Lowen, A., Lakdawala, S., Alwine, J., Casadevall, A., Imperiale, M., . . . Yurochko, A. (2023). Virology under the Microscope-a Call for Rational Discourse. JOURNAL OF VIROLOGY. doi:10.1128/jvi.00089-23

Goodrum, F., Lowen, A. C., Lakdawala, S., Alwine, J., Casadevall, A., Imperiale, M. J., . . . Yurochko, A. (2023). Virology under the Microscope-a Call for Rational Discourse. MSPHERE, 8(2). doi:10.1128/msphere.00034-23

Goodrum, F., Lowen, A., Lakdawala, S., Alwine, J., Casadevall, A., Imperiale, M., . . . Yurochko, A. (2023). Virology under the Microscope-a Call for Rational Discourse. MBIO. doi:10.1128/mbio.00188-23

2022

Whitford, A. L., & Cliffe, A. R. (2022). Key questions on the epigenetics of herpes simplex virus latency. PLOS PATHOGENS, 18(6). doi:10.1371/journal.ppat.1010587

Dochnal, S., Merchant, H. Y., Schinlever, A. R., Babnis, A., Depledge, D. P., Wilson, A. C., & Cliffe, A. R. (2022). DLK-Dependent Biphasic Reactivation of Herpes Simplex Virus Latency Established in the Absence of Antivirals. JOURNAL OF VIROLOGY, 96(12). doi:10.1128/jvi.00508-22

Whitford, A. L., Clinton, C. A., Kennedy, E. B. L., Dochnal, S. A., Suzich, J. B., & Cliffe, A. R. (2022). Ex Vivo Herpes Simplex Virus Reactivation Involves a Dual Leucine Zipper Kinase-Dependent Wave of Lytic Gene Expression That Is Independent of Histone Demethylase Activity and Viral Genome Synthesis. JOURNAL OF VIROLOGY, 96(12). doi:10.1128/jvi.00475-22

2021

Dochnal, S. A., Francois, A. K., & Cliffe, A. R. (2021). De Novo Polycomb Recruitment: Lessons from Latent Herpesviruses. VIRUSES-BASEL, 13(8). doi:10.3390/v13081470

Suzich, J. B., Cuddy, S. R., Baidas, H., Dochnal, S., Ke, E., Schinlever, A. R., . . . Cliffe, A. R. (2021). PML-NB-dependent type I interferon memory results in a restricted form of HSV latency. EMBO REPORTS, 22(9). doi:10.15252/embr.202152547

2020

Cuddy, S. R., Schinlever, A. R., Dochnal, S., Seegren, P. V., Suzich, J., Kundu, P., . . . Cliffe, A. R. (2020). Neuronal hyperexcitability is a DLK-dependent trigger of herpes simplex virus reactivation that can be induced by IL-1. ELIFE, 9. doi:10.7554/eLife.58037

Cuddy, S., Schinlever, A., Dochnal, S., Suzich, J., Kundu, P., Downs, T., . . . Cliffe, A. (2020). Neuronal hyperexcitability is a DLK-dependent trigger of HSV-1 reactivation that can be induced by IL-1. doi:10.1101/2020.04.16.044875

2019

Cliffe, A. R. (2019). DNA Damage Meets Neurotrophin Signaling: A Delicate Balancing AKT to Maintain Virus Latency. MOLECULAR CELL, 74(3), 411-413. doi:10.1016/j.molcel.2019.04.015

2018

Suzich, J. B., & Cliffe, A. R. (2018). Strength in diversity: Understanding the pathways to herpes simplex virus reactivation. VIROLOGY, 522, 81-91. doi:10.1016/j.virol.2018.07.011

2017

Cliffe, A. R., & Wilson, A. C. (2017). Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation. JOURNAL OF VIROLOGY, 91(2). doi:10.1128/JVI.01419-16

2015

Cliffe, A. R., Arbuckle, J. H., Vogel, J. L., Geden, M. J., Rothbart, S. B., Cusack, C. L., . . . Deshmukh, M. (2015). Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation. CELL HOST & MICROBE, 18(6), 649-658. doi:10.1016/j.chom.2015.11.007

2014

Gama, V., Swahari, V., Schafer, J., Kole, A. J., Evans, A., Huang, Y., . . . Deshmukh, M. (2014). The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. SCIENCE SIGNALING, 7(334). doi:10.1126/scisignal.2005309

2013

Cliffe, A. R., Coen, D. M., & Knipe, D. M. (2013). Kinetics of Facultative Heterochromatin and Polycomb Group Protein Association with the Herpes Simplex Viral Genome during Establishment of Latent Infection. MBIO, 4(1). doi:10.1128/mBio.00590-12