NON-HUMAN PRIMATE MODEL OF KAPOSI?S SARCOMA-ASSOCIATED HERPESVIRUS INFECTION

卡波西肉瘤相关疱疹病毒感染的非人灵长类动物模型

• 批准号: 7715514
• 负责人: HEESON CHANG
• 金额: $ 3.24万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715514
• 关键词: Acquired Immunodeficiency Syndrome; Adam11 gene; Animal Model; Antibody Formation; CCL22 gene; Callithrix; Callithrix jacchus jacchus; Cells; Characteristics; Computer Retrieval of Information on Scientific Projects Database; DNA; Dermal; FK506; Funding; Glycoproteins; Grant; Health; Herpesviridae Infections; Human; Human Herpesvirus 8; Immunosuppressive Agents; Infection; Institution; Kaposi Sarcoma; Lesion; Leukocytes; Lymphoma; Modeling; Multicentric Angiofollicular Lymphoid Hyperplasia; Oral; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pleural effusion disorder; Primates; Proteins; Recombinants; Reporting; Research; Research Personnel; Resources; Route; Skin; Source; Time; Tissues; Transplant Recipients; United States National Institutes of Health; chlorambucil/dactinomycin/methotrexate protocol; in vivo; latent nuclear antigen; nonhuman primate; transmission process; viral DNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kaposi's sarcoma associated herpesvirus (KSHV) associates with Kaposi's sarcoma (KS), pleural effusion lymphomas (PEL), and multicentric Castleman's disease (MDC). Despite this significant human health problem, KSHV studies are greatly hampered by the lack of animal model. In here, we report the successful zoonotic transmissions of a KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate, which significantly recapitulates important aspects of KSHV infection in human. Marmosets intravenously inoculated with recombinant KSHV, called rKSHV.219, rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. In addition, KSHV DNA and latent nuclear antigen protein (LANA) were readily detected from the peripheral blood mononuclear cells (PBMCs) and various tissues of infected marmosets at multiple time points. As seen with other immunosuppressant drug that represses KSHV-infected cell growth8 and inhibits the progression of dermal KS in transplant recipients, FK506 immunosuppressant treatment led to a significant reduction of KSHV persistent infection in vivo. Furthermore, marmosets infected with rKSHV.291 by the oral route also seroconverted and were positive for viral DNA in their PBMCs. Remarkably, an orally infected marmoset developed the KS-like skin lesion with characteristic spindle cells and infiltrating leukocytes that was also positive to the KSHV DNA and K8.1 glycoprotein. AIDS related.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 卡波西肉瘤相关疱疹病毒 (KSHV) 与卡波西肉瘤 (KS)、胸腔积液淋巴瘤 (PEL) 和多中心卡斯尔曼病 (MDC) 相关。尽管存在这一重大人类健康问题，但 KSHV 研究因缺乏动物模型而受到极大阻碍。在这里，我们报告了 KSHV 成功传播到新世界灵长类动物普通狨猴 (Callithrix jacchus, Cj) 中的人畜共患传播，这显着概括了人类 KSHV 感染的重要方面。狨猴静脉注射重组 KSHV（称为 rKSHV.219）后，迅速发生血清转化并维持强烈的抗 KSHV 抗体反应。此外，在多个时间点从受感染狨猴的外周血单核细胞 (PBMC) 和各种组织中很容易检测到 KSHV DNA 和潜伏核抗原蛋白 (LANA)。与其他抑制 KSHV 感染细胞生长并抑制移植受者真皮 KS 进展的免疫抑制剂药物一样，FK506 免疫抑制剂治疗可显着减少体内 KSHV 持续感染。此外，通过口服途径感染 rKSHV.291 的狨猴也发生了血清转化，并且其 PBMC 中的病毒 DNA 呈阳性。值得注意的是，经口腔感染的狨猴出现了 KS 样皮肤病变，具有特征性梭形细胞和浸润性白细胞，且 KSHV DNA 和 K8.1 糖蛋白也呈阳性。 艾滋病相关。