DETECTION AND SIGNIFICANCE OF SI VARIANTS OF HIV

艾滋病病毒，导致艾滋病的病毒，在每个人类宿主中迅速进化， HIV中的序列变异性对于疾病进展是重要的。 这项建议的长远目标是研究 HIV序列变异性的意义和后果。 一 这种变异性的例子是合胞体诱导（SI）类 HIV-1在体外能在T淋巴细胞中形成合胞体，并进化为 在50%的HIV-1感染者中， 作为第一个具体的 为了实现这一目标，重组病毒将使用 患者病毒序列以测试其体外表型。 的 待使用的序列已通过V3特异性异源双链体鉴定 作为不具有SI的进化变体的跟踪测定 表型序列与表型的关系 将深入了解SI表型与 疾病进展。 第二个目标是分离SI和非SI 特定病人的基因序列 这些序列将被用作探针 用于来自相同患者的淋巴组织的原位杂交， 检查变异体在淋巴组织中的分布。 其他目标 涉及确定以下因素之间的相关性： 等离子体中的进化变体：1）向SI进化 表型，2）快速疾病进展，和3）抗逆转录病毒药物 治疗失败 V3特异性异源双链追踪试验将在 在所有这些实验中用于检测V3的存在 在循环病毒中的进化变体。

HIV, the virus that causes AIDS, evolves rapidly in each human host and the sequence variability in HIV is important for disease progression. The long-term objectives of this proposal are to examine the significance and consequences of sequence variability in HIV. One example of this variability is the syncytium-inducing (SI) class of HIV-1 that can form syncytia in T lymphocytes in vitro and evolves de novo in 50 percent of HIV-1 infected individuals. As a first specific aim for this proposal, recombinant viruses will be constructed using patient viral sequences to test their in vitro phenotypes. The sequences to be used have been identified by a V3-specific heteroduplex tracking assay as evolutionary variants that do not have the SI phenotype. The relationship between the sequences and their phenotypes will provide insight into the correlation between SI phenotype and disease progression. The second aim is to isolate SI and non-SI sequences from specific patients. The sequences will be used as probes for in situ hybridization of lymphoid tissue from the same patients to examine the distribution of the variants in lymphoid tissue. Other aims involve the determination of the correlation between the presence of evolutionary variants in plasma with: 1) the evolution toward the SI phenotype, 2) rapid disease progression, and 3) antiretroviral drug therapy failure. The V3-specific heteroduplex tracking assay will be used in all of these experiments to detect the presence of V3 evolutionary variants in circulating virus.