Role of IFNe in immune modulation and HIV infection

IFNe在免疫调节和HIV感染中的作用

• 批准号: 10356898
• 负责人: Theresa L Chang
• 金额: $ 60.28万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356898
• 关键词: AIDS prevention; Acute; Biological Response Modifiers; Biopsy; Blood; Cells; Cervical; Chronic; Clinical; Data; Disease; E protein; Effector Cell; Elements; Estrogen Therapy; Estrogens; Exhibits; Exposure to; Female; Gene Expression; Gene Expression Regulation; Genes; Goals; HIV; HIV Infections; HIV Seronegativity; HIV resistance; Human; IFNAR1 gene; Immune; Immune response; Immunity; In Vitro; Infection; Interferon-alpha; Interferons; Knowledge; Mediating; Menstrual cycle; Modeling; Molecular; Molecular Cloning; Mucosal Immunity; Mucous Membrane; Peripheral; Peripheral Blood Mononuclear Cell; Phagocytosis; Plasma; Play; Postmenopause; Predisposition; Process; Production; Property; Publishing; Reactive Oxygen Species; Regulation; Research; Resistance; Role; Sampling; Seminal Plasma; Seminal fluid; Sexually Transmitted Diseases; Signal Transduction; Testing; Tissues; Toll-Like Receptor Pathway; Vagina; Variant; Viral; Viral Load result; Viral Physiology; Viral reservoir; Virus; Woman; cervical biopsy; cervicovaginal; chronic infection; clinically relevant; cohort; cytokine; differential expression; humanized mouse; immune activation; immune function; immunoregulation; in vivo; longitudinal analysis; macrophage; mouse model; prevent; receptor; recruit; reproductive tract; resistant strain; sex; transcriptome; transmission process; virus host interaction

Project Summary Interferon e (IFNe) is a critical innate immune mediator that protects the host against sexually transmitted infections. Although the current paradigm is that IFNε is a type I IFN and signals through IFNa receptors, our and other published results show that IFNε has unique immune functions that are distinct from IFNa/b. IFNε is highly abundant in the mucosa of the female reproductive tract, and has superior mucosal immune activity compared to IFNa/b. IFNe gene expression is regulated by estrogen, cytokines, and seminal plasma, but is not induced by Toll-like receptor pathways, which induce IFNa/b. Clinical evidence indicates a protective role of IFNe against HIV. IFNe expression is positively associated with estrogen levels during the menstrual cycle, and inversely correlates with HIV susceptibility. Importantly, HIV-negative sex workers with frequent exposure to semen have an increased level of IFNe gene expression, and have increased numbers of immune effector cells in cervical tissues. We recently demonstrate that IFNe induces an anti-HIV state through a mechanism independent of known type I IFN-induced HIV host restriction factors in primary macrophages. Additionally, IFNε elicits a more robust immune response than IFNa2. We hypothesize is that IFNe displays a dual role in HIV inhibition by protecting HIV target cells and by modulating immune functions, and will test our hypothesis by determining the immune mechanism of IFNe and its impact on HIV infection in vitro, cervical explants and in humanized mouse model. To gain a better understanding of the molecular mechanism of IFNe-mediated HIV inhibition, we determine viral determinants important for IFNe sensitivity. Because estrogen is known to modulate IFNe expression and mucosal immunity, we will assess the impact of estrogen on IFNε-mediated processes in HIV infection in postmenopausal women before and after estrogen treatment. Elucidating the properties and functions of IFNe promises to expand our knowledge of virus-host interactions crucial for HIV prevention and control of viral reservoirs and immunopathogenesis.

项目总结

项目成果

Differential Effects of Antiseptic Mouth Rinses on SARS-CoV-2 Infectivity In Vitro.

• DOI: 10.3390/pathogens10030272
• 发表时间: 2021-03-01
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Xu C;Wang A;Hoskin ER;Cugini C;Markowitz K;Chang TL;Fine DH
• 通讯作者: Fine DH

Brilacidin, a Non-Peptide Defensin-Mimetic Molecule, Inhibits SARS-CoV-2 Infection by Blocking Viral Entry.

Brilacidin 是一种非肽防御素模拟分子，通过阻止病毒进入来抑制 SARS-CoV-2 感染。

• 发表时间: 2022
• 期刊: EC microbiology
• 作者: Xu,Chuan;Wang,Annie;Honnen,William;Pinter,Abraham;Weston,WarrenK;Harness,JaneA;Narayanan,Aarthi;Chang,TheresaL
• 通讯作者: Chang,TheresaL

Multifaceted immune functions of human defensins and underlying mechanisms.

人防御素和潜在机制的多方面免疫功能。

• DOI: 10.1016/j.semcdb.2018.02.023
• 发表时间: 2019-04
• 期刊: Seminars in cell & developmental biology
• 影响因子: 7.3
• 作者: Fruitwala S;El-Naccache DW;Chang TL
• 通讯作者: Chang TL

Human Immunodeficiency Viruses Pseudotyped with SARS-CoV-2 Spike Proteins Infect a Broad Spectrum of Human Cell Lines through Multiple Entry Mechanisms.

• DOI: 10.3390/v13060953
• 发表时间: 2021-05-21
• 期刊: Viruses
• 作者: Xu C;Wang A;Geng K;Honnen W;Wang X;Bruiners N;Singh S;Ferrara F;D'Angelo S;Bradbury ARM;Gennaro ML;Liu D;Pinter A;Chang TL
• 通讯作者: Chang TL