Cytomegalovirus Infections in Oral Cavity

描述：(申请人提供)人类巨细胞病毒感染，如 作为CMV视网膜炎，占最重要的艾滋病相关因素之一 机会主义的并发症。此外，人巨细胞病毒感染也是最严重的 与艾滋病患者相关的口腔疾病的常见原因。人巨细胞病毒感染 免疫功能低下的患者可能会产生口腔损伤和疼痛的溃疡 据报道，嘴唇、舌头和口腔粘膜都有糜烂。唾液腺 是持久性病毒的主要来源，并已被证明是CMV的场所 潜伏感染。从受感染的唾液中排出的唾液中的病毒 腺体被认为也是口腔感染的主要来源之一。 至于水平传输。对巨细胞病毒感染机制的认识 唾液腺和口腔的其他部分将提供洞察力 开发新药和新的治疗和预防策略 巨细胞病毒相关的口腔疾病。以小鼠巨细胞病毒为模型系统， 这项拟议的研究旨在确定CMV复制所需的病毒基因 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 产生了包含转座子序列的MCMV突变体池，并具有 分离出一株唾液复制缺陷的病毒突变体 腺体。在这项拟议的研究中，动物将被病毒突变体感染 通过直接接种到唾液腺和那些有缺陷的 在唾液腺中复制时会被分离出来。特征描述 这些突变体将被用来识别由 转座子插入及其在组织培养中的生长特性 动物将被决定。最后，分子机制是如何 已确定的病毒决定簇在支持MCMV感染方面发挥作用 唾液腺将被研究。这些研究将导致对 唾液腺中复制CMV所需的病毒基因和 这些基因在口腔巨细胞病毒感染中的功能研究 空洞。此外，这些结果还将为深入了解CMV的发病机制提供依据。 发病机制和治疗和治疗的新策略的发展 预防CMV全身性感染和口腔感染。

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.