Cytomegalovirus Infections in Oral Cavity

描述：（由申请人提供）人巨细胞病毒感染，如 作为CMV视网膜炎，占最重要的艾滋病相关疾病之一， 机会性并发症此外，HCMV感染也是最常见的感染之一。 常见的口腔疾病与艾滋病患者有关。HCMV感染 在免疫功能低下的患者中可能会产生口腔损伤和疼痛性溃疡， 据报道，唇、舌和颊粘膜有糜烂。唾液腺 是持久性病毒的主要来源，并已被证明是CMV的一个位点 潜伏感染唾液中的病毒从受感染的唾液中脱落 腺体也被认为是口腔感染的主要来源之一 至于水平传输。了解CMV感染的机制， 唾液腺以及口腔的其他部分将提供洞察力 开发新的药物和新的策略来治疗和预防 CMV相关的口腔疾病。使用鼠巨细胞病毒作为模型系统， 这项研究的目的是确定CMV复制所需的病毒基因 在唾液腺中，并研究这些病毒决定簇的功能， 支持口腔中的CMV感染。申请人最近 产生了含有转座子序列的MCMV突变体库， 分离出一种在唾液中复制缺陷的病毒突变体， 腺体在拟议的研究中，动物将感染病毒突变体 通过直接接种到唾液腺和那些有缺陷的 在唾液腺中复制的细胞会被分离出来表征 这些突变体将被用来鉴定由突变体引起的基因。 转座子插入和它们在组织培养中的生长特性， 动物将被确定。最后，我们来探讨 确定的病毒决定簇在支持MCMV感染中发挥作用， 将研究唾液腺。这些研究将导致识别 唾液腺中CMV复制所需的病毒基因， 研究这些基因在口腔巨细胞病毒感染中的功能， 腔此外，研究结果将为CMV的发病机制提供新的见解 发病机制和新的治疗策略的发展， 预防CMV全身感染以及口腔感染。

DESCRIPTION: (Provided by Applicant) Infections by human cytomegalovirus, such as CMV retinitis, account for one of the most important AIDS-associate opportunistic complications. Moreover, HCMV infections are also one of the most common causes of oral diseases associated with AIDS patients. HCMV infections in immunocompromised patients may produce oral lesions and painful ulcers and erosions have been reported on lips, tongue, and buccal mucosa. Salivary glands are a major source of persistent virus and have been shown to be a site for CMV latent infections. Viruses in saliva that are shed from infected salivary glands are believed to be one of the major sources for oral infections as well as for horizontal transmission. Understanding the mechanism of CMV infection in salivary glands as well as other parts of the oral cavity will provide insight into developing new drugs and novel strategies for treatment and prevention of CMV-associated oral diseases. Using murine cytomegalovirus as a model system, the proposed study is to identify the viral genes required for CMV replication in salivary glands and to study the functions of these viral determinants in supporting CMV infections in the oral cavity. The applicant has recently generated a pool of MCMV mutants that contain a transposon sequence and has isolated a viral mutant that was defective in replication in the salivary glands. In the proposed research, animals will be infected with viral mutants through direct inoculation to the salivary glands and those that are defective in replicating in the salivary glands will be isolated. Characterization of these mutants will be carried out to identify the genes that are mutated by the transposon insertion and their growth characteristics in tissue culture and in animals will be determined. Finally, the molecular mechanisms of how the identified viral determinants function in supporting MCMV infections in salivary glands will be studied. These studies will lead to the identification of viral genes required for CMV replication in salivary glands and the investigations of the functions of these genes in CMV infections of the oral cavity. Moreover, the results will provide insights into the mechanism of CMV pathogenesis and the development of novel strategies for treatment and prevention of CMV systemic infections as well as infections in the oral cavity.