Molecular structures and replication fitness of HIV-1 intersubtype recombinants

开发抗病毒疗法和有效的HIV-1疫苗的主要障碍是 病毒。重组是导致HIV-1病毒迅速多样化的主要机制 人口。不同亚型HIV-1之间的重组产生亚型间重组体。这些 亚型间重组子也可以与相同或不同亚型的HIV-1或与其他亚型的HIV-1重组 重组体以产生更复杂的重组体。亚型间重组体几乎在每一个 世界上存在一种以上HIV-1亚型的地区。目前，有49例HIV-1病毒正在传播 重组形式(CRF)和大量独特的重组形式(URF)已被鉴定。 这些CRF和URF约占全球感染的20%，它们继续发挥着 在塑造艾滋病大流行方面发挥着越来越重要的作用。 目前的研究重点是HIV-1复制和亚型间的机制和致病基因组学 重组。在这一应用中，我们继续我们的研究，以了解分子机制 产生具有生物学优势的HIV-1亚型间重组子。我们的长期目标是澄清 病毒基因组中影响HIV-1重组体复制适合性的因素。这些病毒成分 代表新的潜在目标，用于阻止或加强可能影响连续重组的重组 HIV-1在宿主体内的复制。本申请的目的是表征分子结构 以及体内产生的HIV-1亚型间重组体的复制适合性。中心假设是 新产生的HIV-1亚型间重组体具有一系列复制适合度，并且存在 HIV-1复制适合性的有限窗口允许重组子继续在宿主中复制。这个 具体目的是1)揭示体内HIV-1亚型间重组体的多样性，2)表征HIV-1亚型间重组体 HIV-1亚型间重组子的复制适合度和3)确定产生的选择压力 具有生物学优势的HIV-1亚型间重组体。我们希望我们的工作将增强我们的 关于产生HIV-1变异和新的HIV-1重组毒株的分子机制的知识。

The main hindrance to develop antiviral therapies and effective vaccines for HIV-1 is the high variability of the virus. Recombination is a major mechanism that is responsible for the rapid diversification of HIV-1 population. Recombination between different subtypes of HIV-1 generates intersubtype recombinants. These intersubtype recombinants can also recombine with HIV-1 of the same or different subtypes or with other recombinants to generate more complex recombinants. Intersubtype recombinants emerge in almost every region of the world where more than one HIV-1 subtype is present. Currently, 49 HIV-1 circulating recombinant forms (CRFs) and a large number of unique recombinant forms (URFs) have been identified. These CRFs and URFs accounted for approximately 20% of global infections and they continue to play an increasingly important role in shaping the AIDS pandemic. iVly current research focuses on the mechanisms and pathogenomics of HIV-1 replication and intersubtype recombination. In this application, we continue our study on understanding the molecular mechanisms for generating HIV-1 intersubtype recombinants with biological advantages. Our long-term goal is to elucidate the elements in the viral genome that affect replication fitness of a HIV-1 recombinant. These viral elements represent new potential targets for blocking or enhancing recombination that can affect the continuous replication of HIV-1 in the host. The objectives of this application are to characterize the molecular structures and the replication fitness of HIV-1 intersubtype recombinants generated in vivo. The central hypothesis is that newly generated HIV-1 intersubtype recombinants have an array of replication fitness and there is a finite window for HIV-1 replication fitness allowing the recombinants to continue to replicate in the host. The Specific Aims are to 1) reveal the diversity of HIV-1 intersubtype recombinants in vivo, 2) characterize the replication fitness of HIV-1 intersubtype recombinants and 3) define the selection pressure for generating HIV-1 intersubtype recombinants with biological advantages. We expect our work will enhance our knowledge on the molecular mechanisms that generate HIV-1 variations and new HIV-1 recombinant strains.