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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Kaposi的肉瘤与Kaposi的肉瘤（KS），胸腔积液淋巴瘤（PEL）和多中心Castleman病（MDC）相关联。尽管存在严重的人类健康问题，但由于缺乏动物模型，KSHV研究受到了极大的阻碍。在这里，我们报告了KSHV成功地向普通的Marmosets（Callithrix Jacchus，CJ）进行的人畜共患传播，这是一种新世界灵长类动物，它显着概括了人类KSHV感染的重要方面。用重组KSHV静脉内接种的Marmoset，称为RKSHV.219，迅速进行血清转化并保持剧烈的抗KSHV抗体反应。此外，从外周血单核细胞（PBMC）和多个时间点感染的果mo虫的各种组织中很容易检测到KSHV DNA和潜在的核抗原蛋白（LANA）。正如其他免疫抑制剂药物抑制了KSHV感染的细胞生长8并抑制了移植受者中真皮KS的进展，FK506免疫抑制剂治疗导致体内KSHV持久性感染显着降低。此外，口腔途径感染了RKSHV.291的摩尔果会也具有血清转化，并且PBMC中的病毒DNA呈阳性。值得注意的是，口服感染的果酱发育于具有特征性纺锤体细胞的KS样皮肤病变和浸润的白细胞，对KSHV DNA和K8.1糖蛋白也呈阳性。 与艾滋病有关。