Human herpes virus

The Varicella Zoster Virus (VZV) naturally infects only humans to cause the common childhood infection chickenpox. Following chickenpox, VZV remains dormant in the nerves for the lifetime of the person. In about 25% of people, VZV becomes active again, travelling down the nerves to cause the painful skin rash known as shingles. Acute shingles rash can be debilitating and is characterised by significant pain which can last for weeks or months, even after the skin rash has healed. If the pain persists for longer than 3 months after the rash has healed is termed post herpetic neuralgia (PHN). Shingles and PHN gets worse in older individuals and in people whose immune systems do not work properly. Importantly the currently available drugs for treating shingles and PHN are suboptimal and although there is a vaccine which prevents shingles and PHN, it only works in 50-65% of subjects. Dr Depledge’s research aims to determine whether there are particular strains of VZV that are more likely to cause PHN. Secondly he aims to understand better the mechanism by which VZV becomes active after many years dormant to cause shingles and PHN.

Dr Depledge will sequence the DNA from over 1500 strains of VZV collected from people with shingles, some of whom had mild pain and others of whom developed severe PHN. This is a unique collection of samples, including some from subjects who were vaccinated with the shingles vaccine, but still developed shingles. From the results he will be able to work out if there are some viral strains that are not controlled by vaccine. This information will be useful for improving design of the vaccine in the future. By comparing VZV from both groups, Daniel plans to identify mutations in the DNA which are more common in those subjects who had PHN. Based on these results, it may be possible to develop tests which will predict which subjects with shingles are more at risk of developing PHN so that they can be given more intensive treatment.

Dr Depledge also plans to sequence DNA from human nerves which have been removed, with permission, from patients a few hours after death. The nerve material is known to contain dormant VZV. Daniel will use specialised sequencing methods known as Chromatin Immunoprecipitation and RNA-Seq, to try to understand how human proteins in the nerves interact with the VZV to prevent it becoming activated and to keep it dormant. Again this work relies on a unique set of samples which have been made available to him by his collaborators. The results will help to identify human proteins that are important for keeping VZV dormant. This is turn will pave the way for the future development of drugs which can interact with the proteins identified to keep the virus dormant and prevent shingles.