Deregulation of host functions and persistence of KSHV

世界上90%以上的人口持续感染多种疱疹病毒。卡波西‘s 肉瘤相关疱疹病毒(KSHV)可在口腔内建立持续性感染，并可 口头传播的。KSHV感染表现为艾滋病患者并导致几种淋巴增生性疾病 疾病以及卡波西肉瘤。尽管宿主细胞和免疫系统已经进化 控制疱疹病毒感染的机制，疱疹病毒也制定了逃避和/或 激怒他们。疱疹病毒利用多个病毒基因来实现精确的基因表达控制和 为了对抗宿主免疫系统，这两个系统都是建立、维持和重新激活所必需的 延迟。在潜伏期和裂解复制之间的成功过渡对于病毒在 主持人。目前还不清楚该病毒如何调节自身的表达和解除管制。 细胞转录，以有效复制和逃避免疫反应。 要了解KSHV的持续机制，主要集中在基因表达水平 监管和免疫规避加州四家实验室联手以下四个项目将是 主要研究内容如下：1)KSHV ORF36抑制干扰素产生的机制 (项目负责人：任，加州大学洛杉矶分校)；2)ORF36作为唯一的病毒激酶转录调控作用 KSHV(项目负责人：龚兴健，加州大学戴维斯分校)；3)两个KSHV编码的机制 先天免疫途径的调节剂(ORF10和ORF45)(项目负责人Don Ganem，加州大学旧金山分校)；4) 检测KSHV持续感染的非人灵长类动物模型的建立 ORF10、ORF36、K-bZIPPRF45和K5K3在体内病毒感染中的免疫逃避作用 领导者：Jae Jung，哈佛/南加州大学)。

More than 90% of the world population is persistently infected with several herpesviruses. Kaposi's sarcoma-associated herpesvirus (KSHV) can establish persistent infection in the oral cavity and can be transmitted orally. KSHV infection manifests in AIDS patients and leads to several lymphoproliferative diseases as well as Kaposi's sarcoma. Although the host cells and the immune system have evolved mechanisms to control herpesviral infections, herpesviruses have also developed strategies to evade and/or antagonize them. Herpesviruses employ multiple viral genes to achieve precise gene expression control and to counteract the host immune system, both of which are essential to establish, maintain, and reactivate from latency. The successful transition between latency and lytic replication is critical for viral persistence in the host. It has not been clearly understood about how the virus regulates its own expression and deregulates cellular transcription to efficiently replicate and evade immune responses. To understand the mechanisms of KSHV persistence, concentrated on at the level of gene expression regulation and immune evasion, four laboratories in California join forces. The following four projects will be primarily addressed: 1) the mechanism of inhibition on type inhibiting interferon production by KSHV ORF36 (project leader: Ren Sun, UCLA); 2) the transcriptional regulatory role of ORF36 as the sole viral kinase of KSHV (project leader: Hsing-Jien Kung, UC Davis); 3) the mechanism underlying two KSHV-encoded modulators (ORF10 and ORF45) of innate immune pathways (Project leader, Don Ganem, UCSF); 4) development of develop a non-human primate model for the KSHV persistent infection of KSHV to determine the immune evasive role of ORF10, ORF36, K-bZIPPRF45 and K5K3 during viral infection in vivo (Project leader: Jae Jung, Harvard/USC).