HIV INHIBITORY SALIVARY MOLECULES--GENES & MECHANISMS

HIV抑制唾液分子——基因

• 批准号: 2458668
• 负责人: HAL E. BROXMEYER
• 金额: $ 20.39万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458668
• 关键词: AIDS; HIV envelope protein gp120; HIV infections; T cell receptor; binding proteins; chemokine; clinical research; complementary DNA; genetic library; helper T lymphocyte; human immunodeficiency virus 1; human subject; laboratory mouse; laboratory rabbit; macrophage; monocyte; nucleic acid sequence; parotid gland; polymerase chain reaction; secretory immune system; sublingual gland; submandibular gland; virus infection mechanism; virus protein; virus replication

DESCRIPTION: (adapted from applicant's abstract): Previous research has recognized that saliva contains factors which inhibit HIV-1 production or infectivity. The salivary HIV-inhibitory factors (SHIF) can be derived from salivary glands and immune systems such as lymphocytes and macrophages. Four hypotheses will be tested in the proposal: 1) There are unidentified SHIFs in addition to the reported factor such as secretory leukocyte protease-inhibitor (SLPI); 2) certain SHIFs (HIV bp) bind to viral envelop proteins and inhibit viral entry; 3) chemokines constitute one of SHIF; and 4) certain SHIFs compete with HIV-1 for receptors on T cells, or monocytes. To test the hypotheses, five specific aims are proposed. 1. To isolate and characterized SHIF cDNA from a subtractive expression cDNA libraries of parotid and submandibular/sublingual salivary glands. 2. To isolate and characterize cDNAs whose protein products (HIV bp) bind to HIV-1 gp120, from parotid and submandibular salivary gland cDNA libraries by yeast-based two-hybrid system. 3. To determine whether normal or AIDS patient's saliva contain macrophage or T cell-derived chemokines which display HIV-1-suppressive activities. 4. To determine whether the binding of HIV bp to gp120 inhibits HIV-1 attachment or subsequent stages of HIV-1 life cycle. 5. To determine whether certain SHIF such as chemokines and SLPI compete with HIV-1 for the binding to CD4+ T cells or monocytes, or inhibit other stage of HIV-1 life cycle. Identification of natural HIV-inhibitory defectors and determination of their action mechanisms are necessary for effective treatment of AIDS. Since individual isolates of HIV-1 shows difference in sensitivity to a certain inhibitory factors, identification of more inhibitory factors will aid in developing treatment modalities of AIDS.

描述：（改编自申请人的摘要）：先前的研究 认识到唾液包含抑制HIV-1产生或 感染力。 唾液HIV抑制因素（SHIF）可以从 唾液腺和免疫系统，例如淋巴细胞和巨噬细胞。 提案中将检验四个假设：1）身份不明 除报告因子（例如分泌白细胞）外 蛋白酶抑制剂（SLPI）； 2）某些SHIF（HIV BP）与病毒包膜结合 蛋白质并抑制病毒式进入； 3）趋化因子构成SHIF之一；和 4）某些SHIF与HIV-1竞争T细胞或单核细胞上的受体。 为了检验假设，提出了五个具体目标。 1。从减法表达中分离和表征SHIF cDNA 腮腺和下颌/舌下唾液腺的cDNA库。 2。分离和表征其蛋白质产物（HIV BP）结合的cDNA 到HIV-1 GP120，来自腮腺和下颌下唾液腺cDNA库 通过基于酵母的两种杂交系统。 3。确定正常还是艾滋病患者的唾液是否包含巨噬细胞 或T细胞衍生的趋化因子，显示HIV-1抑制活性。 4。确定HIV BP与GP120的结合是否抑制HIV-1 HIV-1生命周期的依恋或随后的阶段。 5。确定某些SHIF（例如趋化因子和SLPI）是否竞争 与HIV-1结合与CD4+ T细胞或单核细胞的结合，或抑制其他 HIV-1生命周期的阶段。 鉴定自然艾滋病毒抑制剂并确定 它们的作用机制对于有效治疗艾滋病是必要的。 由于HIV-1的单个分离株显示出对A的敏感性差异 某些抑制因素，识别更多抑制因素将 有助于开发艾滋病的治疗方式。