Understanding human cytomegalovirus latency as a means to target the latent reservoir

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Human cytomegalovirus (HCMV) is a type of herpesvirus which is carried without symptoms by the majority of the population. However, it can cause serious disease in infants born to mothers who acquire the infection in pregnancy. Similarly, in people whose immune systems are suppressed, for instance when they undergo organ transplantation or stem cell grafts, HCMV can be life threatening. There has been a continual call for increases in the number of transplants in the UK (see http://www.bbc.co.uk/news/health-40564329 and http://www.bbc.co.uk/news/health-11688102); this means that HCMV disease is likely to become more and more of a problem, particularly, in transplant patients.Unlike many other viruses, HCMV is never cleared after its initial infection but persists for the life-time of the individual. At least in part, this is due to the ability of HCMV to avoid the immune system by expression of virus genes which help it avoid immune responses. However, the life-long persistence of this virus is also a biological property of all herpesviruses because the virus is able to undergo a so-called latent infection. During latency, the virus hides in the cell without making new virus particles but is still able to reawaken, generating new infectious virus which can cause disease and can also be passed on to other uninfected people. Understanding how the virus succeeds in maintaining itself as a latent infection in people without causing disease and how this relationship breaks down to cause disease should help develop better methods of treating the virus and for designing a vaccine (there is currently no vaccine available). Our research is aimed at determining (i) the mechanisms by which the virus maintains a silent infection (latency) in specialised cells of the immune system (ii) how the virus re-awakens (reactivation) and (ii) how the immune system is prevented from eliminating the virus from the body. This will help us understand how the virus is able to hijack the cell in order for the virus to be carried latently and will inform us of novel therapies to target latently infected cells to prevent disease in transplant patients. In addition to advancing our understanding of HCMV, in particular, this research may also lead to a better understanding of other virus infections which persist in the body, how the human host controls them as well as help identify common strategies for their elimination.