A High-throughput Strategy to Identify HIV Intra-subtype Recombinant Sequences

鉴定 HIV 亚型内重组序列的高通量策略

• 批准号: 8653766
• 负责人: Ming Zhang
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653766
• 关键词: Address; Antiviral Therapy; Complex; Confidence Intervals; Detection; Disease Progression; Drug resistance; Epidemic; Evolution; Foundations; Genetic; Genetic Recombination; Genome; Geographic Locations; HIV; HIV-1; Length; Light; Methodology; Methods; Modeling; Molecular Epidemiology; Molecular Evolution; Mutation; Nucleotides; Organism; Patients; Phylogenetic Analysis; Prevalence; Probability; Publishing; Quantitative Evaluations; Recombinants; Research; Research Proposals; Scheme; Vaccine Therapy; Vaccines; Viral; Virus; Work; base; design; disease transmission; driving force; epidemiology study; experience; genome sequencing; improved; markov model; novel; public health relevance; repaired; viral detection

DESCRIPTION (provided by applicant): Intra-subtype recombination is an efficient strategy applied by HIV-1 (human immunodeficiency virus type 1) to generate extraordinary virus diversity that contributes to intra-patient quasi-species and drug resistance. Here we propose a novel methodology to detect HIV-1 intra-subtype recombination to fill the gap between the necessity of tracking HIV genetic changes along disease progression and transmission and lack of intra-subtype analysis methodologies. Due to greater sequence similarity, intra-subtype recombination is harder to detect than inter-subtype recombination. Therefore the detection of intra- subtype recombination, not only in the HIV case but also in other organisms, should consider appropriate array of sequences that can reflect a full spectrum of diversity within a subtype. In this regard, we hypothesize that these sequences have existed more abundantly in sequenced fragments but are less present in sequenced complete genome sequences, while the latter are widely used in any kind of HIV recombination studies. Our rationale derives from our previous study, in which we successfully identified sub-subtypes within HIV-1 subtype J. Our findings were based on sequenced fragments rather than complete genome sequences. We believe that the repertoire of all published sequence fragments contains a great degree of sequence diversity that we have overlooked in many aspects of studies, including viral molecular evolution and molecular epidemiology studies. The objective of this project is to (1) identify sub-subtype representative sequences within each HIV-1 subtype; and (2) implement a high-throughput scheme for detection of viral intra-subtype recombination. Our proposed study will provide a basis for a rational and quantitative evaluation of the prevalence of HIV-1 intra-subtype recombinants, which is critical for tracking the dynamic and complex HIV epidemic and designing improved antiviral therapies and vaccines. Last but not the least, our proposed research strategy can also be applied to the recombination study in other viruses.

描述（由申请人提供）：亚型内重组是 HIV-1（人类免疫缺陷病毒 1 型）应用的一种有效策略，用于产生非凡的病毒多样性，有助于患者内的准物种和耐药性。在这里，我们提出了一种检测 HIV-1 亚型内重组的新方法，以填补跟踪疾病进展和传播过程中 HIV 遗传变化的必要性和缺乏亚型内分析方法之间的空白。由于序列相似性较高，亚型内重组比亚型间重组更难检测。因此，亚型内重组的检测，不仅在 HIV 病例中，而且在其他生物体中，都应考虑能够反映亚型内全谱多样性的适当序列阵列。在这方面，我们假设这些序列在测序片段中更丰富地存在，但在测序的完整基因组序列中较少存在，而后者广泛用于任何类型的HIV重组研究。我们的基本原理源自我们之前的研究，在该研究中，我们成功鉴定了 HIV-1 J 亚型中的亚型。我们的发现基于测序片段，而不是完整的基因组序列。我们相信，所有已发表的序列片段都包含很大程度的序列多样性，而我们在许多研究方面都忽视了这些多样性，包括病毒分子进化和分子流行病学研究。该项目的目标是 (1) 确定每个 HIV-1 亚型内的亚亚型代表性序列； (2)实施高通量方案来检测病毒亚型内重组。我们提出的研究将为合理和定量评估 HIV-1 亚型内重组体的流行率提供基础，这对于跟踪动态和复杂的 HIV 流行以及设计改进的抗病毒疗法和疫苗至关重要。最后但并非最不重要的一点是，我们提出的研究策略也可以应用于其他病毒的重组研究。