Role of Monocytes in AIDS and as Targets for Antiviral Therapy

单核细胞在艾滋病中的作用及其作为抗病毒治疗的靶标

• 批准号: 6104610
• 负责人: Sharon M Wahl
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 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/6104610
• 关键词: AIDS therapy; HIV infections; Mycobacterium avium; Pneumocystis carinii; antiviral agents; comorbidity; helper T lymphocyte; human immunodeficiency virus 1; human tissue; in situ hybridization; laboratory mouse; macrophage; monocyte; protease inhibitor; saliva; secretory immune system; virus RNA; virus infection mechanism; virus replication

Despite the presence of HIV-1 in the oral cavity, transmission of the virus through saliva is rare which implicates innate/natural antiviral mechanisms for suppressing transmission. One such endogenous antiviral molecule, secretory leukocyte protease inhibitor (SLPI), inhibits HIV-1 infection of mononuclear cells during or soon after internalization. To further clarify the function of SLPI in innate/host defense, efforts are underway to generate mice homozygous for a null mutation of SLPI. In additional studies focusing on the regulation of HIV production after infection, opportunistic pathogens were shown to influence viral replication. By in situ hybridization, unprecedented levels of HIV were detected in co-infected tissues. Mycobacterium avium promotes HIV infection by activating the transcription factor NF-kappaB, stimulating cytokine and chemokine production and HIV co-receptor (CCR5) expression. The dynamic relationship between opportunistic pathogens, macrophages and high levels of viral replication emphasize that treatment of co-infections is important for controlling HIV production and plasma viremia, particularly in late-stage HIV-disease. In addition to opportunistic pathogens, mucosal inflammation also exacerbates HIV production and therapeutic intervention dramatically reduces viral burden, emphasizing the negative contribution of immune activation to the clinical course of AIDS.

尽管口腔中存在HIV-1，但 病毒通过唾液传播很少见 抑制传播的先天/天然抗病毒机制。 一种这样的内源性抗病毒分子，分泌白细胞 蛋白酶抑制剂（SLPI），抑制了单核的HIV-1感染 内在化期间或不久之后。进一步阐明 SLPI在先天/宿主防御中的功能，正在进行努力 生成纯合的小鼠，以使SLPI的无效突变。在 侧重于调节艾滋病毒的其他研究 感染后，显示机会病原体会影响 病毒复制。通过原位杂交，前所未有的水平 在共感染的组织中检测到HIV。分枝杆菌 通过激活转录因子促进HIV感染 NF-kappab，刺激细胞因子和趋化因子的产生以及 HIV共受体（CCR5）表达。动态关系 机会性病原体，巨噬细胞和高水平 病毒复制强调，共同感染的治疗是 对于控制HIV产生和血浆病毒血症的重要性很重要， 特别是在晚期HIV疾病中。除了机会主义 病原体，粘膜炎症也加剧了艾滋病毒的产生 和治疗干预大大减轻了病毒负担， 强调免疫激活对 艾滋病的临床过程。