Human Herpesvirus Impact on Periodontal Inflammation

人类疱疹病毒对牙周炎的影响 Afsar Raza Naqvi博士 人类疱疹病毒（HHV）是一种大的、有包膜的DNA病毒，具有终身潜伏期。 在成年人中，持续检测到一种或多种类型的病毒，表明HHV 人体内的适应。多条证据表明，这些疾病的患病率较高， 但HHV如何加重这些感染仍是一个未知数。 未开发的与其他病毒不同，HHV的一个独特特征是它们也编码病毒性 miRNAs（v-miRs）。这些病毒microRNA（vmiRs）是多功能的，因为它们调节 病毒和宿主衍生的转录物的表达，从而控制宿主-病毒相互作用。在 在这个建议中，我们将研究五种最常见的口腔炎症疾病的影响。 相关的HHV即，HCMV、HSV-1、EBV、KSHV和HHV-6B对牙周炎的影响， 非常常见的口腔炎性疾病。病毒miRNA的水平将在 患者患病牙龈与病毒基因组和生命周期相关 成绩单我们的目的是表征候选vmiRs在调节HHV感染中的作用， 宿主牙龈上皮细胞和巨噬细胞。识别积极和消极的监管V- miR可以产生对宿主-病毒相互作用的新见解。vmiRs对关键生物学特性的影响 原代人口腔角化细胞和巨噬细胞的功能将主要通过 评价它们对针对周围病原体（牙龈卟啉单胞菌和A. 放线菌属（actinomycetemcomitans）。这将为病毒-细菌协同作用提供新的见解。我们的下一个目标 将测试vmiRs是否会使宿主免疫系统功能失调。这将由 增强巨噬细胞和树突细胞中vmiR的表达。关键的生物功能 这些细胞包括病原体摄取，抗原加工和呈递给T辅助细胞（CD4+） 和T细胞毒性（CD8+）细胞。此外，我们将评估v-miR对极化的影响， CD4 + T细胞生成的数据将为现有知识提供重要信息 差距。有趣的是，由于vmiR不是内源性RNA，因此它们具有被部署的潜力。 作为潜在的治疗靶点。鉴于其免疫调节作用，操纵这些小的 RNA还可用于口腔炎性疾病的诊断和治疗。

Human Herpesvirus Impact on Periodontal Inflammation Afsar Raza Naqvi, Ph.D. Human Herpesviruses (HHV) are large, enveloped DNA viruses that establish lifelong latency. In adult humans, one or more types of viruses are persistently detected signifying HHV adaptation inside human body. Multiple lines of evidence show higher prevalence of these viruses in various oral inflammatory diseases but how HHV exacerbate these infections remains unexplored. A unique feature of HHV, unlike other viruses, is that they also encode viral miRNAs (v-miRs). These viral microRNAs (vmiRs) are multifunctional as they regulate expression of both virus and host derived transcripts and thus control host-virus interaction. In this proposal, we will study the impact of five most common oral inflammatory diseases associated HHV viz., HCMV, HSV-1, EBV, KSHV and HHV-6B on periodontal inflammation, a highly common oral inflammatory disease. The levels of viral miRNAs will be quantified in patients with diseased gingiva and correlate with viral genome and life cycle associated transcripts. We aim to characterize the role of candidate vmiRs in regulating HHV infection in host gingival epithelial cells and macrophages. Identifying positive and negative regulatory v- miRs can yield novel insights into host-virus interaction. The impact of vmiRs on key biological functions of primary human oral keratinocytes and macrophages will be examined primarily by evaluating their influence on innate response against periopathogens (P. gingivalis and A. actinomycetemcomitans). This will shed novel insights into virus-bacterial synergy. Our next aim will test whether vmiRs can render host immune system dysfunctional. This will be examined by enforced expression of vmiRs in macrophages and dendritic cells. The key biological functions of these cells include pathogen uptake, antigen processing and presentation to T helper (CD4+) and T cytotoxic (CD8+) cells. In addition, we will assess the impact of v-miRs on the polarization of CD4+ T cells. The data generated will provide significant information to existing knowledge gaps. Interestingly, as vmiRs are not endogenous RNAs, they have the potential to be deployed as potential therapeutic targets. Given their immunomodulatory role, manipulation of these small RNAs may also be useful in the diagnosis and treatment of oral inflammatory diseases.