MICROBICIDAL AGENTS FOR HSV AND HIV-1--IN VITRO STUDIES

在这个项目中，来自芝加哥(西北大学)三个地点的调查人员 大学医学院、芝加哥大学医学中心和拉什- 长老会-圣彼得堡Luke‘s Medical Center)提出合作研究 单纯疱疹病毒1型和2型(HSV-1和HSV-2)和人类 免疫缺陷病毒1型(HIV-1)。的主要目标之一 这个项目是为了确定在治疗中有效的抗菌剂 预防HSV-1、HSV-2和HIV-1感染培养细胞。这个 培养的细胞类型将包括那些常规用于体外培养的细胞 传染性研究(HeLa细胞用于HSV和外周血单核细胞 HIV的细胞[PMNC])以及从 女性生殖道(主要是取自上皮的细胞 宫颈和邻近的阴道)。候选抗菌剂 包括硫酸盐多糖，因为它们可能阻止 HSV和HIV-1与细胞和表面活性物质的结合 预计会破坏这些病毒的包膜。第二个重要的 项目1的目标是探索细胞和病毒的决定因素 女性原代培养的人细胞感染HSV和HIV-1的实验研究 生殖道，以评估要求是否相似 与已经为永久细胞系建立的细胞系相同或不同。 其具体目的是(I)评价其疗效和细胞毒性。 预防HSV-1、HSV-2和HIV-1的潜在局部杀微生物剂 感染上述培养的细胞类型；(Ii)产生突变 HSV-1和HSV-2的致病株，以获得 影响HeLa细胞和其他永久性细胞系的能力受损； 以及(Iii)评估HSV亲本株和突变体以及选定的HSV株 HIV-1感染原代培养的人类细胞 女性生殖道，处理前和处理后的AAT细胞 预计会改变或掩盖病毒的细胞受体。单纯疱疹病毒 此项目中生成的突变体也将在项目3中用于 旨在确定豚鼠致病性决定因素的研究 生殖器感染模型。从这三起案件中获得的信息来看 项目，我们将确定最有效的杀微生物剂 保护女性生殖道的细胞和组织免受 感染艾滋病毒-1、单纯疱疹病毒和衣原体，将定义一些关键 在这些人中建立感染的细胞和病毒决定因素 细胞和组织。

In this project, investigators from three sites in Chicago (Northwestern University Medical School, University of Chicago Medical Center, and Rush- Presbyterian-St. Luke's Medical Center) propose collaborative studies on herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and human immunodeficiency virus type 1 (HIV-1). One of the principal objectives of this project is to identify antimicrobial agents that are effective in preventing the infection of cultured cells by HSV-1, HSV-2 and HIV-1. The cultured cell types will include those used routinely for in vitro infectivity studies (HeLa cells for HSV and peripheral blood mononuclear cells [PMNC] for HIV) as well as primary human cells cultured from the female preproductive tract (principally cells obtained from the epithelium of the cervix and adjacent vagina). The candidate antimicrobial agents include sulfated polysaccharides selected for their potential to block the binding of HSV and HIV-1 to cells and surface-active agents that are expected to damage the envelopes of these viruses. A second important objective of project 1 is to explore the cellular and viral determinants for HSV and HIV-1 infection of primary human cells cultured from the female reproductive tract, in order to assess whether the requirements are similar to or different from those already established for permanent cell lines. The specific aims are to (i) evaluate the efficacy and cytotoxicity of potential topical microbicides in prevention of HSV-1, HSV-2 and HIV-1 infection of cultured cell types as outlined above; (ii) generate mutants of pathogenic strains of HSV-1 and HSV-2 to obtain strains that are impaired in ability to affect HeLa cells and other permanent cell lines; and (iii) evaluate HSV parental strains and mutants and selected strains of HIV-1 for their ability to infect primary human cells cultured from the female reproductive tract, before and after treatments of athe cells that are predicted to alter or mask cell receptors for the viruses. The HSV mutants generated in this project will also be used in project 3 for studies designed to define determinants of pathogenicity in the guinea pig model of genital infection. From the information obtained in all three projects, we will identify the microbicide that are most effective in protecting cells and tissues of the female reproductive tract against infection by HIV-1, HSV and chlamydia and will define some of the key cellular and viral determinants for establishment of infection in these cells and tissues.