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型(HHV8)与恶性肿瘤有关，特别是在免疫抑制的患者中，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)密切相关，MCD是一种侵袭性淋巴增生性疾病。KSHV在肿瘤和PEL细胞系中的感染主要是潜伏的，病毒DNA以多拷贝EB病毒形式持续存在。KSHV在显性感染中表达的基因数量有限，且潜伏基因表达的程序在不同的恶性肿瘤中有所不同。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在男男性行为中既有性传播，也有非性传播，但其具体传播方式仍有待阐明。口腔传播与KSHV有关，可能是性途径和非性途径感染的原因。与口服传播一致，在唾液中发现高水平的KSHV DNA，但在精液、前列腺液或粪便中未发现。此外，唾液中含有传染性的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提示，溶血性感染在口腔中的作用可能比在KSHV相关肿瘤中更突出。值得注意的是，在活体内，最近从患者口腔粘膜刮取的浅表角质形成细胞中发现了KSHV感染。然而，口咽腔内KSHV潜伏感染和裂解感染的详细分析仍有待进行。本工作将对口咽腔内KSHV的生物学进行研究。将确定KSHV感染的地点(S)，并确定每个地点的感染性质。将确定感染KSHV的细胞类型，并确定KSHV基因在不同细胞类型中的潜伏和裂解表达模式。此外，还将建立KSHV感染原代口腔角质形成细胞的体外系统。这样的系统应该有助于今后对KSHV口咽感染的研究。

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.