HIV-Host Interactions

随着成人、儿童和青少年艾滋病毒-1感染继续在世界各地传播，进一步抗逆转录病毒治疗的开发仍然至关重要；例如，没有有效的艾滋病毒-1疫苗，目前针对病毒逆转录酶和蛋白酶的一线治疗因依从性、毒性和病毒耐药性问题而受到影响。因此，寻求其他HIV-1(或人类)蛋白质作为未来抗病毒药物的靶标是至关重要的，但它们的合理选择需要对潜在的生物学原理有基本的理解。专性细胞内寄生虫的复制，如HIV-1，依赖于许多宿主衍生因子和途径的贡献。然而，包括我们自己在内的许多实验室最近的研究表明，宿主细胞也会产生本质上抗病毒的因子，并能够对抗病毒的生长。本工作主要从三个方面对细胞进行研究--S抗HIV-1天然武库。首先，我们将继续研究人类APOBEC3G/F蛋白，以及它们如何不仅通过抑制病毒基因组的复制，而且通过引入致命突变来抑制感染。其次，我们将从APOBEC3蛋白对细胞生理学的贡献方面探索APOBEC3蛋白的生物学，并研究与APOBEC3蛋白相互作用的细胞因子(如RNA沉默机制)，或积累在与细胞相似的位置上的细胞因子对病毒复制的贡献。第三，我们将从基因表达的变化和抗病毒机制的潜在动员方面描述人类T细胞对HIV-1初始入侵的反应，并将其与广泛抗病毒的1型干扰素的效果进行比较和对比。任何刺激这些已证实的/潜在的抗病毒机制的治疗策略都有可能打破促进和抑制活动之间的平衡，从而在人与人之间传播或已确定的感染的背景下抑制艾滋病毒-1感染。九龙总公司的公共关系部主要负责向公众宣传我们的工作；专家名录？使公众能够找到愿意讨论专业领域的学者。例如，MHM接受了媒体的多次采访，出现在电视上，并就艾滋病相关节目的内容接受了BBC的咨询。他也是公共获取期刊《公共科学图书馆·病原体》的分部编辑，曾在社区联络会议(如Cafe Science fique)上就科学研究的价值举行概述研讨会，并帮助组织艾滋病毒/艾滋病社区非科学成员参加的会议。

As adult, paediatric and adolescent HIV-1 infections continue to spread worldwide, the development of further anti-retroviral treatments remains of the utmost importance; for instance, there is no effective HIV-1 vaccine, and current front-line therapies targeting the viral reverse transcriptase and protease enzymes are compromised by compliance, toxicity and viral resistance concerns. Pursuing other HIV-1 (or human) proteins as targets for future anti-virals is therefore critical, but their rational selection requires a fundamental understanding of underlying biological principles. The replication of obligate intracellular parasites, such as HIV-1, is dependent upon the contributions of many host-derived factors and pathways. However, recent work from many laboratories, including our own, has shown that host cells also produce factors that are intrinsically anti-viral and are able to antagonise virus growth. This work focuses on three aspects of the cell?s natural armoury against HIV-1. First, we will continue our investigation of human APOBEC3G/F proteins, and how they suppress infection not only by inhibiting the copying of the viral genome, but also by introducing lethal mutations. Second, we will explore the biology of APOBEC3 proteins in terms of their contributions to cell physiology, and examine the contributions of cellular factors that interact with APOBEC3 proteins (such as the RNA silencing machinery), or accumulate in similar sites with cells, to virus replication. Third, we will characterise the response of human T cells to initial invasion by HIV-1 in terms of alterations in gene expression and the potential mobilisation of anti-viral mechanisms, and compare and contrast this effects with those of the broadly anti-viral type-1 interferons. Any therapeutic strategy that stimulates these proven/potential anti-viral mechanisms has the possibility of tipping the balance between facilitatory and inhibitory activities and thereby suppressing HIV-1 infection in the context of transmission between humans or established infection. The Public Relations Dept of KCL is primarily responsible for communicating our work to the public; and a ?Directory of Experts? is maintained that enables members of the public to identify academics willing to discuss specialist areas. For instance, MHM has given numerous interviews to the press, has appeared on television and has been consulted by the BBC on the content of AIDS-related programming. He is also a Section Editor of a public access journal, PLoS Pathogens, has given overview seminars on the value of scientific research at Community Liaison Meetings (e.g., Cafe Scientifique), and helps organise Conferences attended by non-scientific members of the HIV/AIDS community.