Deregulation of host functions and persistence of KSHV

超过90%的世界人口持续感染几种疱疹病毒。卡波西 肉瘤相关疱疹病毒（KSHV）可在口腔中建立持续性感染， 口头传播。艾滋病患者出现KSHV感染并导致多种淋巴组织增生 疾病以及卡波西肉瘤。尽管宿主细胞和免疫系统已经进化到 除了控制疱疹病毒感染的机制之外，疱疹病毒还开发了逃避和/或 对抗他们。疱疹病毒利用多个病毒基因来实现精确的基因表达控制， 抵抗宿主免疫系统，这两者对于建立，维持和重新激活免疫系统至关重要。 延迟。潜伏期和裂解性复制之间的成功转换对于病毒在细胞中的持久性至关重要。 主持人关于病毒如何调节自身的表达和解除调节， 细胞转录以有效地复制和逃避免疫应答。 为了了解KSHV持续存在的机制，集中在基因表达水平上 监管和免疫逃避，四个实验室在加州联手。以下四个项目将 主要阐述：1）KSHV ORF 36抑制型干扰素产生的抑制机制 （项目负责人：Ren Sun，UCLA）; 2）ORF 36作为唯一的病毒激酶的转录调节作用， KSHV（项目负责人：Hsing-Jien Kung，加州大学戴维斯分校）; 3）两个KSHV编码的 先天免疫途径的调节剂（ORF 10和ORF 45）（项目负责人，Don Ganem，UCSF）; 4） 建立非人灵长类动物KSHV持续感染模型，以确定KSHV ORF 10、ORF 36、K-bZIPPRF 45和K5 K3在体内病毒感染期间的免疫逃避作用（项目 主持人：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).