DEVELOPMENTAL VIROLOGY

发育病毒学

• 批准号: 3791340
• 负责人: SHALOM Z HIRSCHMAN
• 金额: --
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3791340
• 关键词: AIDS; DNA replication; HIV infections; antiAIDS agent; clinical trials; drug resistance; enzyme linked immunosorbent assay; female; genetic recombination; genetic transcription; helper T lymphocyte; hepatitis; hepatitis B; hepatitis B virus group; human immunodeficiency virus; human subject; molecular cloning; monocyte; nucleic acid hybridization; nucleic acid sequence; nucleoside analog; opportunistic infections; serology /serodiagnosis; tissue /cell culture; virus DNA; virus antigen; virus classification; virus genetics; virus replication; virus virus interaction

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection share similar epidemiologic features; moreover both viruses require reverse transcription for replication. During studies to examine the possible role played by HBV in the development of AIDS, two extrachromosomal 3.2kb DNAs hybridizing to HBV DNA were cloned from the peripheral blood mononuclear cell (PBMC) DNAs of HIV infected patients. One of the clones appears to be typical HBV DNA; however the other clone hybridized to both HBV and HIV DNA probes. A major objective of this proposal is to survey the various populations of HIV-infected patients in our medical school complex, especially those patients in the various ACTU protocols, for the presence of HBV-related sequences in PBMCs. We want to determine whether correlations exist between the presence of HBV-related DNA with stage of the HIV infection; the numbers of CD4+ cells; the clinical course of the HIV infection; the presence of neurologic disease; the presence of various opportunistic infections; the presence of various neoplasias; the response to the various therapies, including those of the ACTG protocols; and the isolation of HIV strains resistant to the various therapeutic agents such as AZT, ddC and ddI. Experiments will be performed to determine whether the HBV-related DNA is cell associated or found in the supernatants of the PBMC cultures of HIV-infected patients, in the free state or in particulate forms. PBMCs containing the HBV-related DNA will be examined for the location of the DNA, whether cytoplasmic or intranuclear; the expression of HBV antigens; and the expression of HBV and HIV-HBV homologous transcripts. The cellular subtype that harbors the HBV-recombinant DNA, whether T4, T8 or non-T cell will be determined. Experiments will be performed to examine the effect of HIV on the replication of HBV DNA in PBMCs and H9 cells. The major questions to be addressed by these studies are: 1) can data be garnered to implicate HBV as a cofactor in the progression of HIV infection to AIDS; 2) does the presence of HBV DNA in the PBMCs affect the clinical course of HIV infection including the response to treatment; 3) does treatment of HIV infection with nucleoside analogues affect the presence of HBV DNA in the PBMCs; 4) does HIV facilitate the replication of HBV DNA in mononuclear cells; and 5) what are the correlates of the presence of apparent HIV-HBV recombinant DNA molecules in PBMCs of HIV-infected patients and what are some of the molecular characteristics of the replication of this apparent recombinant molecule in PBMCs and H9 cells?

丙型肝炎病毒（HBV）和人类免疫缺陷病毒（HIV）感染 具有类似的流行病学特征；而且，这两种病毒都需要逆转 复制的转录。 在研究期间检查可能的作用 由HBV在艾滋病的开发中扮演，两个外肌体3.2kb DNA 将杂交与HBV DNA从外周血单核克隆 HIV感染患者的细胞（PBMC）DNA。 其中一个克隆似乎是 典型的HBV DNA；但是，另一个克隆与HBV和HIV DNA杂交 探针。 该提案的主要目的是调查各种 我们医学院综合大楼中的HIV感染患者人群， 尤其是各种ACTU方案中的患者 PBMC中与HBV相关的序列的。 我们想确定是否 HBV相关DNA与阶段的存在之间存在相关性 艾滋病毒感染； CD4+细胞的数量；临床课程 艾滋病毒感染；神经疾病的存在；存在各种 机会性感染；存在各种肿瘤；反应 对各种疗法，包括ACTG方案的疗法；和 分离抗各种治疗剂的艾滋病毒菌株 作为AZT，DDC和DDI。 将进行实验以确定是否 与HBV相关的DNA与细胞相关或发现 在自由状态或颗粒中，HIV感染患者的PBMC培养物 表格。 将检查包含HBV相关DNA的PBMC的PBMC。 DNA的位置，无论是细胞质还是核内；表达 HBV抗原；以及HBV和HIV-HBV同源转录本的表达。 携带HBV重组DNA的细胞亚型，无论是T4，T8 或将确定非T细胞。 将进行实验以检查 HIV对PBMC和H9细胞中HBV DNA复制的影响。 这 这些研究要解决的主要问题是：1）数据可以是 获得HBV作为艾滋病毒感染进展的辅助因子 艾滋病； 2）PBMC中HBV DNA是否存在影响临床 HIV感染过程，包括对治疗的反应； 3）做 用核苷类似物治疗HIV感染会影响 PBMC中的HBV DNA； 4）HIV是否有助于HBV DNA的复制 单核细胞； 5）存在的相关性是什么 HIV感染的PBMC中明显的HIV-HBV重组DNA分子 患者和哪些分子特征是 在PBMC和H9细胞中复制这种明显的重组分子？