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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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)和多中心性Castleman病(MDC)相关。尽管存在这一重大的人类健康问题，但由于缺乏动物模型，KSHV的研究受到很大阻碍。在这里，我们报道了KSHV成功地传播到常见的绒猴(Callithrix Jacchus，CJ)，这是一种新世界的灵长类动物，极大地概括了KSHV在人类感染的重要方面。静脉接种重组KSHV(称为rKSHV.219)的恒河猴能迅速进行血清转换，并保持较强的抗KSHV抗体反应。此外，在多个时间点，从感染猴的外周血单核细胞(PBMCs)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皮肤KS进展的免疫抑制药物一样，FK506免疫抑制治疗显著减少了KSHV在体内的持续感染。此外，经口服途径感染rKSHV.291的猕猴也出现血清转换，其PBMC中病毒DNA呈阳性。值得注意的是，口服感染的绒猴出现了KS样皮肤病变，其特征是梭形细胞和浸润性白细胞，KSHV DNA和K8.1糖蛋白也呈阳性。与艾滋病有关。