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

人巨细胞病毒（HCMV）是一种疱疹病毒，大多数人携带时没有症状。然而，它可能会导致严重的疾病，婴儿出生的母亲谁获得感染怀孕。同样，在免疫系统受到抑制的人中，例如当他们接受器官移植或干细胞移植时，HCMV可能危及生命。在英国，人们一直呼吁增加移植手术的数量（见http://www.bbc.co.uk/news/health-40564329和http：//www.bbc.co.uk/news/health-11688102）;这意味着HCMV疾病可能成为越来越严重的问题，特别是在移植患者中。与许多其他病毒不同，HCMV在初次感染后从未被清除，而是在个体的一生中持续存在。至少在某种程度上，这是由于HCMV通过表达病毒基因来避免免疫系统的能力，这有助于它避免免疫应答。然而，这种病毒的终身持续性也是所有疱疹病毒的生物学特性，因为该病毒能够经历所谓的潜伏感染。在潜伏期，病毒隐藏在细胞中，不产生新的病毒颗粒，但仍然能够重新唤醒，产生新的感染性病毒，可以引起疾病，也可以传递给其他未感染的人。了解这种病毒如何成功地维持自身作为潜伏感染而不引起疾病，以及这种关系如何破坏而引起疾病，应该有助于开发更好的治疗病毒和设计疫苗的方法（目前没有可用的疫苗）。我们的研究旨在确定（i）病毒在免疫系统的专门细胞中保持沉默感染（潜伏期）的机制（ii）病毒如何重新唤醒（重新激活）以及（ii）如何防止免疫系统将病毒从体内清除。这将帮助我们了解病毒如何能够劫持细胞，以便潜伏携带病毒，并将告知我们针对潜伏感染细胞的新疗法，以预防移植患者的疾病。除了促进我们对HCMV的理解，特别是，这项研究还可能导致更好地了解其他病毒感染，这些病毒感染在体内持续存在，人类宿主如何控制它们，以及帮助确定消除它们的共同策略。

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.