HIV INHIBITORY SALIVARY MOLECULES--GENES & MECHANISMS

HIV抑制唾液分子——基因

基本信息

批准号：
2897138
负责人：
HAL E. BROXMEYER
金额：
$ 21.63万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-30 至 2000-07-31
项目状态：
已结题

项目摘要

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。