The well-known childhood disease chickenpox is caused by infection with Varicella Zoster Virus (VZV). During a chickenpox episode, VZV also invades the nervous system before switching into state of latency. Latency is analogous to hibernation and is usually maintained throughout life, although periodic reactivation (reawakening of the virus) can cause painful bouts of the related disease, Shingles, typically in older individuals. Shingles can be accompanied by various complications, including persistent pain (lasting for months or years) and, rarely, encephalitis (swelling of the brain). Understanding how VZV causes these diseases, and especially how the virus switches into and out of latency, is vitally important if we are to improve treatment options and effectiveness. Dr Daniel Depledge (University College London) and Dr Tomohiko Sadaoka (Kobe University) met while Dr Sadaoka was working at the National Institutes of Health in the USA as they embarked with colleagues on a collaborative VZV project in 2015. This led to an important scientific breakthrough in how to mimic VZV entry into, and exit from, latency (http://www.pnas.org/content/113/17/E2403.abstract). A unique aspect of this research was the combination of two pioneering techniques, one developed by Dr Sadaoka, the other by Dr Depledge, to provide new insights into the disease mechanisms.
Dr Depledge received a Small Grant from the Daiwa Anglo-Japanese Foundation that supported a month-long visit to Kobe University where he and Dr Sadaoka were able to further develop their techniques and collaborations. The primary aim of their current project is to explore how VZV latency affects the nerve cells in which they reside. Experiments carried out at Kobe University included (i) establishing an improved nerve cell culture system, (ii) infecting nerve cells with VZV under controlled conditions and using specialised techniques to enforce viral latency, and (iii) harvesting nerve cell and viral genetic material (DNA and RNA) at various times for analysis using the latest sequencing technologies. Their project yielded two key outcomes: Firstly, new data were acquired from a unique experimental setup that is now being analysed with the aim of providing new and unique insights into VZV infections. These data will inform future experimental design and provide the basis for a new research proposal. Secondly, the success of this visit has reinforced future collaborations between these two scientists that will enable them to build upon the existing innovative work for many years and solve outstanding VZV infection treatment and prevention questions.