Molecular structures and replication fitness of HIV-1 intersubtype recombinants

HIV-1亚型间重组体的分子结构和复制适应性

• 批准号: 8534074
• 负责人: Po San Mario Chin
• 金额: $ 22.43万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8534074
• 关键词: AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Affect; Antiviral Therapy; Award; Biological; Cell Culture Techniques; Complex; Elements; Genetic Recombination; Goals; HIV-1; Human; Indium; Infection; Instruction; Knowledge; Molecular; Molecular Structure; Phase; Play; Population; Public Health; Recombinants; Research; Role; Shapes; Vaccines; Variant; Viral; Viral Genome; Virus; Work; fitness; in vivo; pandemic disease; pressure; prevent; AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Affect; Antiviral Therapy; Award; Biological; Cell Culture Techniques; Complex; Elements; Genetic Recombination; Goals; HIV-1; Human; Indium; Infection; Instruction; Knowledge; Molecular; Molecular Structure; Phase; Play; Population; Public Health; Recombinants; Research; Role; Shapes; Vaccines; Variant; Viral; Viral Genome; Virus; Work; fitness; in vivo; pandemic disease; pressure; prevent

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.

开发抗病毒疗法和HIV-1有效疫苗的主要障碍是 病毒。重组是导致HIV-1快速多元化的主要机制 人口。 HIV-1不同亚型之间的重组会产生subtype的重组。这些 Intersubtype重组者还可以与相同或不同亚型的HIV-1或其他相同的HIV-1或其他 重组以产生更复杂的重组。几乎每一个 世界上存在多种HIV-1亚型的地区。目前，49 HIV-1循环 已经确定了重组形式（CRF）和大量独特的重组形式（URF）。 这些CRF和URF占全球感染的20％，它们继续发挥 在塑造艾滋病大流行方面越来越重要的作用。 当前的研究重点是HIV-1复制的机制和病原体学和Intersubtype 重组。在此应用中，我们继续研究了解分子机制 产生具有生物学优势的HIV-1间的重组。我们的长期目标是阐明 病毒基因组中影响HIV-1重组的复制适应性的元素。这些病毒元素 代表阻止或增强重组的新潜在目标，可能会影响连续的 主机中HIV-1的复制。该应用的目标是表征分子结构 以及HIV-1的复制适应性在体内产生的重组体。中心假设是 新生成的HIV-1 InterSubType重组剂具有一系列复制适应性，并且有一个 HIV-1复制健身的有限窗口，使重组者可以继续在主机中复制。这 具体目的是1）在体内揭示HIV-1 Intersubtype重组的多样性，2）表征 HIV-1 Intersubtype重组者的复制适合度和3）定义生成的选择压力 具有生物学优势的HIV-1间型重组剂。我们希望我们的工作将增强我们的 了解产生HIV-1变异和新的HIV-1重组菌株的分子机制的知识。