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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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Castleman病（MDC）相关。尽管存在这一重大的人类健康问题，但KSHV研究因缺乏动物模型而受到极大阻碍。在这里，我们报告了成功的人畜共患传播的KSHV到普通绒猴（Callithrix jacchus，Cj），一个新的世界灵长类动物，这显着概括了重要方面的KSHV感染人类。静脉接种重组KSHV（称为rKSHV.219）的绒猴迅速发生血清转化，并保持强烈的抗KSHV抗体应答。此外，KSHV DNA和潜伏核抗原蛋白（拉娜）很容易检测到从外周血单个核细胞（PBMC）和各种组织的感染的绒猴在多个时间点。与其他抑制KSHV感染细胞生长8和抑制移植受体皮肤KS进展的免疫抑制剂一样，FK 506免疫抑制剂治疗可显著降低体内KSHV持续感染。此外，通过口服途径感染rKSHV.291的绒猴也发生血清转化，并且在其PBMC中病毒DNA呈阳性。值得注意的是，一只经口感染的绒猴出现了KS样皮肤病变，具有特征性的梭形细胞和浸润性白细胞，这些细胞对KSHV DNA和K8.1糖蛋白也呈阳性。 与艾滋病有关。

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.