2021 EF Jonathan Cleaver

Dr Jonathan Cleaver

2023 ABN Fellowship

The immunobiology of herpes simplex virus encephalitis and post-infectious antibody-mediated disease

Encephalitis is a serious condition whereby the brain becomes swollen and inflamed. Herpes simplex virus is its leading cause with an untreated death rate of 70%, reducing to around one-quarter with early treatment. In one-quarter of patients the illness can return leading to further severe health problems.

In recent times, the role of the immune system following herpes simplex virus encephalitis (HSE) has become increasingly recognised as a possible cause for such disability. The immune system may become confused and mistakenly attack the brain further whilst trying to control the virus. Therefore, controlling the immune system’s inflammatory reaction may help limit additional brain swelling. This is a valuable but underexplored area of research.

My work, in the world-renowned Oxford Autoimmune Neurology Group, will apply emerging knowledge of unwanted inflammation by the immune system, to its role in HSE. We will study different compartments of the body where the immune system may first be activated to explore direct mechanisms behind its disruption.

Our findings will explore whether tailored treatment targeting the immune system in HSE may help patients with this condition in the future. We will complete this work within three years and communicate our findings to researchers and the public through publications in journals, conference presentations and patient-public engagement days.

2023 ABN Jonathan Cleaver Figure 1

Figure 1 – Possible mechanism of secondary brain inflammation post-herpes simplex virus encephalitis

The deep cervical (or neck) lymph nodes are implicated as the primary peripheral lymphatic drainage site from the meningeal lymphatics of the central nervous system following HSE. We demonstrate a schematic overview of immune cell reactions within neck lymph nodes and their subsequent migration to cause antibody-mediated brain inflammation.

HSV, herpes simplex virus; NMDAR, N-methyl-D-aspartate receptor; GC, germinal centre; BBB, blood-brain barrier; CXCL13, Chemokine (C-X-C motif) ligand 13; ASC, antibody-secreting cell; Ab, antibody


The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity

Cleaver J, Jeffery K, Klenerman P, Lim M et al.

Brain, 2023;, awad419, https://doi.org/10.1093/brain/awad419