Host Defense Regulation and Viral Oncogenesis

宿主防御调节和病毒肿瘤发生

• 批准号: 8546182
• 负责人: Glen N. Barber
• 金额: $ 104.49万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-14 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546182
• 关键词: Address; Adult; Antiviral Agents; Antiviral Therapy; Area; Biological Models; Cause of Death; Chronic; Clinical Trials; Collaborations; Comprehension; Comprehensive Cancer Center; Data; Disease; Doctor of Medicine; Doctor of Philosophy; Epstein-Barr Virus Infections; Florida; Future; Genes; Grant; HIV; Head; Herpesviridae; Host Defense; Host Defense Mechanism; Human; Human Herpesvirus 4; Human Herpesvirus 8; Human T-lymphotropic virus 1; Immune; Immune response; Individual; Infection; Interferon Type I; Interferons; Kaposi Sarcoma; Light; Malignant - descriptor; Malignant Neoplasms; Mediating; Natural History; Natural Immunity; Non-Hodgkin' s Lymphoma; Oncogenic; Oncolytic viruses; Oncornaviruses; Pathway interactions; Patients; Pharmacotherapy; Play; Positioning Attribute; Process; Production; Proteins; Regulation; Research Personnel; Resistance; Role; Satellite Viruses; Signal Pathway; Signal Transduction; Signaling Molecule; Source; T-Cell Leukemia; T-Lymphocyte; Taxes; Translating; Universities; Vaccine Design; Vaccines; Viral; Virus; Virus Diseases; Zidovudine; arm; clinical remission; cohort; combat; design; helicase; improved; interferon therapy; medical schools; member; multidisciplinary; novel; novel therapeutic intervention; novel therapeutics; oncology; oncology program; professor; programs; prophylactic; research study; tumor; tumorigenesis; viral resistance

DESCRIPTION (provided by applicant): Viruses are considered the second most important cause of malignant disease in humans, contributing up to 14-20% of all cancers worldwide. Human cancers associated with virus infection include adult T-cell leukemia (ATLL- human T-cell lymphotropic virus infection; HTLV-1 infection), non-Hodgkins lymphoma (Epstein-Barr Virus; EBV infection) and kaposi's sarcoma (human herpes virus 8; HHV8 infection). A leading cause of death in HIV-infected individuals is also caused by malignant disease induced by selected viral infection. The University of Miami (UM) School of Medicine is in a unique position to study these increasingly prevalent malignant disorders. Essentially, Southern Florida is an endemic area for viral-associated cancers and has the largest cohorts of patients with such diseases in the world. Given this situation, we have assembled a team of investigators at the University of Miami School of Medicine, Sylvester Comprehensive Cancer Center (SCCC), UM, experts in their respective fields of viral oncology and the regulation of host defense. These are Glen N. Barber, Ph.D., William Harrington Jr., M.D., Enrique Mesri, Ph.D., and Ed Harhaj, Ph.D. All are members of the Viral Oncology Program, SCCC, co-headed by Professors Harrington and Barber. Our proposal focuses on overlapping strengths prevalent within our group and takes advantage of our expertise in analyzing host defense and the importance of the interferon (IFN) pathway in naturally combating viral and malignant disease. For example, we have recently elucidated a toll-independent arm of innate immune signaling, essential for the induction of IFN and subsequent expression of anti-viral and anti-tumor genes. These important signaling pathways now appear, unsurprisingly, to be targeted by a growing number of viruses, consequences that may explain mechanisms of viral resistance to IFN therapy, latency and speculatively tumorigenesis. Our proposal focuses on further studying innate immune signaling mechanisms critical for effective host defense. Our study also encompasses the regulation of these processes by the oncoviruses HTLV-1, HHV8 and EBV. More specifically, our proposal comprises three major components: PROJECT I, Glen N. Barber, Ph.D.: Mechanisms of host defense and regulation by oncoviral encoded gene products. PROJECT II, William Harrington, Jr., M.D.: Host Defense regulation by HTLV-1. PROJECT III, Enrique Mesri, Ph.D.: HHV8 (KSHV)-Mediated Regulation of Host Defense.

描述（由申请人提供）：病毒被认为是人类恶性疾病的第二重要原因，占全世界所有癌症的 14-20%。与病毒感染相关的人类癌症包括成人 T 细胞白血病（ATLL-人类 T 细胞淋巴细胞病毒感染；HTLV-1 感染）、非霍奇金淋巴瘤（EB 病毒；EBV 感染）和卡波西肉瘤（人类疱疹病毒 8） HHV8 感染）。 HIV感染者死亡的一个主要原因也是由选定的病毒感染引起的恶性疾病引起的。迈阿密大学 (UM) 医学院在研究这些日益流行的恶性疾病方面处于独特的地位。从本质上讲，南佛罗里达州是病毒相关癌症的流行地区，并且拥有世界上最大的此类疾病患者群。鉴于这种情况，我们在迈阿密大学医学院西尔维斯特综合癌症中心（SCCC）组建了一个研究小组，他们是各自病毒肿瘤学和宿主防御调节领域的专家。他们是 Glen N. Barber 博士、William Harrington Jr. 医学博士、Enrique Mesri 博士和 Ed Harhaj 博士。他们都是 SCCC 病毒肿瘤学项目的成员，该项目由 Harrington 和 Barber 教授共同领导。我们的提案侧重于我们团队内普遍存在的重叠优势，并利用我们在分析宿主防御方面的专业知识以及干扰素 (IFN) 途径在自然对抗病毒和恶性疾病中的重要性。例如，我们最近阐明了先天免疫信号传导的不依赖于 toll 的臂，这对于诱导 IFN 以及随后的抗病毒和抗肿瘤基因的表达至关重要。毫不奇怪，这些重要的信号传导途径现在似乎成为越来越多病毒的目标，其后果可能解释病毒对干扰素治疗的耐药机制、潜伏期和推测的肿瘤发生。我们的建议重点是进一步研究对有效宿主防御至关重要的先天免疫信号机制。我们的研究还包括肿瘤病毒 HTLV-1、HHV8 和 EBV 对这些过程的调节。更具体地说，我们的提案包括三个主要部分：项目 I，Glen N. Barber 博士：肿瘤病毒编码基因产物的宿主防御和调节机制。项目 II，William Harrington, Jr.，医学博士：HTLV-1 的宿主防御调节。项目 III，Enrique Mesri 博士：HHV8 (KSHV) 介导的宿主防御调节。

项目成果

Banerjee P, Tripp A, Lairmore MD, Crawford L, Sieburg M, Ramos JC, Harrington W Jr, Beilke MA, Feuer G. Adult T-cell leukemia/lymphoma development in HTLV-1-infected humanized SCID mice. Blood. 2010;115(13):2640-2648.

Banerjee P、Tripp A、Lairmore MD、Crawford L、Sieburg M、Ramos JC、Harrington W Jr、Beilke MA、Feuer G。HTLV-1 感染的人源化 SCID 小鼠中成人 T 细胞白血病/淋巴瘤的发展。

• 发表时间: 2014-07-10
• 影响因子: 20.3

Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia.

将溶瘤性水泡性口炎病毒重新靶向人类 T 细胞嗜淋巴细胞病毒 1 型相关成人 T 细胞白血病。

• 发表时间: 2015-12
• 作者: Betancourt, Dillon;Ramos, Juan Carlos;Barber, Glen N
• 通讯作者: Barber, Glen N