Early Events in KSVH Infection of Primary B-cells

描述（由申请人提供）：卡波西肉瘤相关疱疹病毒（KSHV/HHV-8）与许多人类癌症有关，特别是艾滋病相关的卡波西肉瘤（KS）和胸腔积液淋巴瘤（PELs）。已知软腭KS以及主要累及身体和四肢是HIV免疫低下人群中与艾滋病发病相关的常见症状。这已经成为一种流行病，KS和胸腔积液淋巴瘤现在被列为发展中国家艾滋病毒感染者死亡的主要原因。KSHV是在15年前被发现的，主要是在个人调查员的水平上解决的。本申请的重点是将宾夕法尼亚大学社区内的3个杰出研究小组聚集在一起，共同研究KSHV介导的肿瘤发生机制。总体目标将是研究在原代B细胞感染的早期阶段通过编码抗原进行病毒控制的机制。在这些早期阶段针对的基本细胞过程将为病毒成功建立潜伏期的严格要求提供新的信息。

DESCRIPTION (provided by applicant): Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8) is associated with a number of human cancers in particular AIDS associated Kaposi sarcoma (KS) and pleural effusion lymphomas (PELs). KS of the soft palate as well as major involvement of the body and extremities has been known to be a common symptom associated with the onset of AIDS in the HIV immunocompromised population. This has become a pandemic and KS as well as pleural effusion lymphomas are now included as the leading causes of death in the HIV population in developing countries. KSHV was identified 15 years ago and has been tackled mostly on a level of the individual investigator. The focus of this application is to bring together 3 prominent groups of investigators within the University of Pennsylvania community to join their scientific expertise to address the mechanism of KSHV mediated oncogenesis. The overall goal will be to investigate the mechanism of viral control by encoded antigens during the early stages of infection of primary B cells. The fundamental cellular processes targeted during these early stages will provide novel new information as to the strict requirements for successful establishment of latency by the virus. The program consists of three scientific projects, an administrative core, a recombineering virus and vector core and a ChIP sequencing core. The scientific projects are: 1. The Role of the RBPJk-LANA complex during early infection; 2. KSHV abortive replication following de novo infection; 3. Chromatin regulation of KSHV during early infection of primary B-cells. The success of these projects will allow for the establishment of a more comprehensive mechanistic view of KSHV infection and pathogenesis and provide new clues for the development of strategies to prevent and treat KSHV associated cancers in the HIV population. In addition the accumulation of new information on KSHV biology will be critical for the broader area of herpesvirus biology with insights into the mechanism of oncogenesis associated with other viruses including EBV and so reducing the burden of disease in the HIV infected, transplants and other immunocompromised population