Oral biology of the Kaposi's sarcoma-associated herpesvirus

卡波西肉瘤（KS）相关疱疹病毒（KSHV）或人类疱疹病毒8（HHV 8）与恶性肿瘤有关，特别是在免疫抑制患者中，包括艾滋病患者。KSHV与KS、原发性渗出性淋巴瘤（PEL）和多中心Castleman病（MCD）（一种侵袭性淋巴组织增生性疾病）密切相关。KSHV在肿瘤和PEL细胞系中的感染主要是潜伏的，病毒DNA作为多拷贝附加体持续存在。KSHV在显性感染中表达的基因数量有限，并且潜伏基因表达程序在不同的恶性肿瘤中不同。裂解性KSHV感染发生在肿瘤和PEL细胞系中的一小部分细胞中。虽然流行病学数据表明，KSHV既可在男男性行为者中通过性传播，也可通过非性传播，但其具体传播方式仍有待阐明。口腔传播与KSHV有关，可以解释性和非性感染途径。与口腔传播一致，唾液中发现高水平的KSHV DNA，但精液、前列腺分泌物或粪便中没有。此外，唾液含有感染性KSHV，因为病毒可以在体外传播到293细胞。唾液中高水平的KSHV DNA表明，溶解性感染可能在口腔中比在KSHV相关肿瘤中具有更突出的作用。值得注意的是，体内KSHV感染最近已显示在从患者口腔粘膜刮下的浅表角质形成细胞中。然而，KSHV潜伏和溶解性感染口咽腔的详细分析仍有待进行。这项工作将调查KSHV在口咽腔的生物学。将确定KSHV感染部位，并确定每个部位的感染性质。将确定感染KSHV的细胞类型，并确定不同细胞类型内潜伏性和裂解性KSHV基因表达的模式。此外，还将开发KSHV感染原代口腔角质形成细胞的体外系统。这样的系统将有助于今后KSHV口咽感染的调查。

Kaposi's sarcoma (KS) associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is associated with malignancies, especially in immune suppressed patients including those with AIDS. KSHV is tightly linked to KS, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD), an aggressive lymphoproliferative disorder. KSHV infection in tumors and PEL cell lines is predominantly latent, with viral DNA persisting as a multicopy episome. KSHV expresses a limited number of genes in patent infection and the program of latent gene expression varies in different malignancies. Lytic KSHV infection occurs in a small percentage of cells in both tumors and PEL cell lines. Although epidemiological data indicates that KSHV is transmitted both sexually among men who have sex with men and also non sexually, its specific mode of transmission remains to be elucidated. Oral transmission have been implicated for KSHV and could account for both sexual and non sexual routes of infection. Consistent with oral transmission,, high levels of KSHV DNA are found in saliva but not semen, prostatic secretions or stool. Further, saliva contains infectious KSHV since virus could be transmitted in vitro to 293 cells. The high levels of KSHV DNA in saliva suggest that lytic infection may have a more prominent role in the oral cavity than in KSHV associated tumors. Of note, in vivo KSHV infection has recently been shown in superficial keratinocytes scraped from the oral mucosa of patients. However, a detailed analysis of KSHV latent and lytic infection in the oropharyngeal cavity remains to be performed. This work will investigate the biology of KSHV in the oropharyngeal cavity. Site(s) of KSHV infection will be identified and the nature of the infection at each site will be determined. Cell types infected with KSHV will be defined and patterns of both latent and lytic KSHV gene expression within different cell types will be determined. In addition, an in vitro system of KSHV infection of primary oral keratinocytes will be developed. Such a system should facilitate future investigations of KSHV oropharyngeal infection.