Chang Heesoon, Wachtman Lynn M, Pearson Christine B, Lee Jong-Soo, Lee Hye-Ra, Lee Steven H, Vieira Jeffrey, Mansfield Keith G, Jung Jae U
Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, California, United States of America.
PLoS Pathog. 2009 Oct;5(10):e1000606. doi: 10.1371/journal.ppat.1000606. Epub 2009 Oct 2.
Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) was first identified in Kaposi's sarcoma (KS) lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA) were readily detected in the peripheral blood mononuclear cells (PBMCs) and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells.
自从卡波西肉瘤相关疱疹病毒（KSHV，即人类疱疹病毒8型）首次在患有艾滋病的HIV感染个体的卡波西肉瘤（KS）病变中被发现以来，人们对KSHV的基本生物学认识有了显著进展。然而，缺乏合适的KSHV动物模型仍然阻碍了对病毒复制、持续性和发病机制的直接体内研究。为了满足对KSHV感染动物模型的这一需求，我们探索了普通狨猴是否能被人类KSHV实验性感染。在此，我们报告了KSHV成功地人畜共患传播到普通狨猴（Callithrix jacchus，Cj），一种新大陆灵长类动物。感染重组KSHV的狨猴迅速发生血清转化，并维持了强烈的抗KSHV抗体反应。在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（LANA）。值得注意的是，一只经口感染的狨猴出现了类似KS的皮肤病变，其特征是KSHV DNA和蛋白质呈阳性的梭形细胞对白细胞进行特征性浸润。这些结果表明，人类KSHV感染普通狨猴，建立了有效的持续性感染，并偶尔导致类似KS的皮肤病变。这是第一个能显著阐述人类KSHV感染重要方面的动物模型，将有助于未来设计针对KSHV的疫苗以及针对KSHV共感染肿瘤细胞的抗病毒疗法。
