Research summary
Human Cytomegalovirus (HCMV) remains a major clinical complication in a number of settings including immune-suppressed transplant patients and following congenital infection. The ability of HCMV, like all herpes viruses, to establish a lifelong latent infection of the host results in the threat posed by HCMV as twofold: Transplant patients are at risk following primary infection or following the reactivation of the latent virus that resides in the recipient.
Our group is part of the CMV research group (with Prof Griffiths) and is focussed on dissecting the molecular basis of HCMV latency and reactivation as well as the role of host cell functions during lytic infection. Questions we are addressing include:
1) The contribution of both viral and cellular functions to viral latency with particular emphasis on how cell signalling pathways are important during both the establishment and reactivation phases of the latent infection.
2) The natural history of HCMV in solid organ transplant patients. Here the focus is to understand the role of viral genetics and host immunity in the onset of viraemia in these patients with a view to a clearer understanding of why certain individuals are at increased risk of HCMV pathogenesis post transplant.
3) The mechanistic basis of protection afforded by the HCMV gB vaccine. A number of HCMV vaccines have been developed but none are licensed to date. The gB vaccine has shown partial protection in 3 phase II trials and now the challenge is to understand why it was protective and how we can make it better. By extension, we will use this to learn about the role of gB in the entry process of HCMV.
4) The development of novel strategies to target HCMV therapeutically. A major aspect of this approach is to use these as tool compounds to probe the biology of HCMV and gain new insight into the biology of the host:pathogen interaction. One aspect is to utilise an anti-viral approach that empowers a more effective response by the humoral immune system.
Although HCMV is our primary focus we are also interested in other pathogens that cause disease. BK polyoma virus is a major pathogen in Kidney transplant recipients. It is a poorly understood pathogen with limited treatment options. We are translating our knowledge of HCMV in transplantation to try and understand the pathogenesis of BK in vivo.
Finally, we are also applying our knowledge obtained studying humoral immunity to the HCMV vaccine to support ongoing studies of the SARS-CoV-2 virus (the aetiological agent of Covid-19). Specifically, with the generous support of a UCL philanthropic fund, we are establishing expertise at the Royal Free to support diagnostic and vaccine assessment capabilities so urgently needed in the current pandemic.
We are indebted to the Medical Research Council, Wellcome Trust, NIHR, Rosetrees and Stoneygate Trusts, the Royal Free Charity and the UCL philanthropic fund who generously support the research carried out in our laboratory.