Regulation of Gammaherpesviral Late Gene Expression

摘要 疱疹病毒在人类群体中是地方性的，并导致广泛的危及生命的疾病。 β疱疹病毒和伽马疱疹病毒亚家族的成员在 免疫功能受损的个体，导致严重的先天性疾病和各种癌症。这 一项提案将定义一类关键的疱疹病毒基因在卡波西病生命周期的后期如何表达 肉瘤相关疱疹病毒(KSHV)通过一种涉及新的转录复合体的机制， 它结合了病毒模仿和选定宿主机制的共同选择。病毒所需的一组蛋白质 晚期基因激活在贝塔病毒和伽马疱疹病毒中广泛保守，表明 本文获得的关于KSHV的信息可能适用于Epstein-Barr病毒和人类巨细胞病毒 也是。这项资助的重点是确定这种新的基因表达的组成和调节。 复杂，并揭示其功能是如何与病毒基因组复制联系在一起的。考虑到即使是细微的突变 这种晚期的基因转录复合体有效地杀死了病毒，了解了它的组成和 预计监管将揭示抗病毒策略的新目标。

ABSTRACT Herpesviruses are endemic within the human population, and cause a wide range of life-threatening diseases. Members of the betaherpesvirus and gammaherpesvirus subfamilies are extremely problematic in immunocompromised individuals, leading to severe congenital disorders and a variety of cancers. This proposal will define how a critical class of herpesviral genes are expressed late in the lifecycle of Kaposi's sarcoma-associated herpesvirus (KSHV) through a mechanism that involves a novel transcription complex, which combines both viral mimicry and co-option of select host machinery. The set of viral proteins required for late gene activation are broadly conserved among the beta- and gammaherpesviruses, indicating that information gained herein for KSHV will likely be applicable for Epstein-Barr virus and human cytomegalovirus as well. The focus of this grant is to define the composition and regulation of this novel gene expression complex, and reveal how its function is linked to viral genome replication. Given that even subtle mutations in this late gene transcription complex effectively `kill' the virus, an understanding of its composition and regulation is anticipated to reveal new targets for antiviral strategies.