Human cytomegalovirus: changes in the latently infected cell as chemotherapeutic and immunological targets for antiviral therapy

人类巨细胞病毒（HCMV）是一种疱疹病毒，大多数人群携带无症状。然而，对于怀孕期间感染的母亲所生的婴儿和免疫系统受到抑制的人来说，它可能会导致严重的疾病，例如，当他们接受肾脏或骨髓等器官移植时，它可能会危及生命。由于缺乏合适的移植器官，每天有多达3人死亡，这导致英国呼吁增加移植数量（http://www.bbc.co.uk/news/health-11688102）， HCMV疾病可能成为移植患者越来越多的问题。与许多其他病毒不同，HCMV在初次感染后永远不会被清除，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有能力通过表达病毒基因来避开免疫系统，从而帮助它避开免疫反应。然而，这种病毒的终生持久性也是所有疱疹病毒的一个生物学特性，因为这种病毒能够经历所谓的潜伏感染，即病毒隐藏在细胞中，不产生新的病毒颗粒，但仍然能够重新苏醒，产生新的传染性美德，这些传染性美德可以引起疾病，也可以传播给其他未感染的人。了解病毒如何成功地在大多数人体内维持自身而不引起疾病，以及这种关系如何破裂而导致疾病，应该有助于开发更好的治疗病毒的方法和设计疫苗（目前没有可用的疫苗）。我们的研究旨在确定(i)病毒在免疫系统的特定细胞中保持沉默感染（潜伏期）的机制，以及这些细胞如何帮助病毒重新唤醒（再激活），以及（ii）如何阻止免疫系统将病毒从体内清除。除了促进我们对HCMV的理解外，这项研究还可能有助于更好地了解在体内持续存在的其他病毒感染，人类宿主如何控制并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 and in people whose immune systems are suppressed, for instance when they undergo transplantation for an organ such as a kidney or bone marrow it can be life threatening. The fact that up to 3 people are dying a day because of a lack of a suitable transplant organs and this is resulting in a call for increases in the number of transplants in the UK (http://www.bbc.co.uk/news/health-11688102), HCMV disease is likely to become more and more of a problem 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 lifelong persistence of this virus is also a biological property of all herpesviruses because the virus is able to undergo a so-called latent infection, where the virus hides in the cell without making new virus particles but is still able to reawaken, generating new infectious virtues which can cause disease and can also be passed on to other uninfected people. Understanding how the virus succeeds in maintaining itself in most 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 mechanism by which the virus maintains a silent infection (latency) in specialised cells of the immune system and how these help the virus reawaken (reactivation) and (ii) how the immune system is prevented from eliminating the virus from the body.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 and help identify common strategies for their elimination.