Zhong W, Wang H, Herndier B, Ganem D
Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6641-6. doi: 10.1073/pnas.93.13.6641.
Kaposi sarcoma (KS) is the leading neoplasm of HIV-infected patients and is also found in several HIV-negative populations. Recently, DNA sequences from a novel herpesvirus, termed KS-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8) have been identified within KS tissue from both HIV-positive and HIV-negative cases; infection with this agent has been proposed as a possible factor in the etiology or pathogenesis of the tumor. Here we have examined the pattern of KSHV/HHV-8 gene expression in KS and find it to be highly restricted. We identify and characterize two small transcripts that represent the bulk of the virus-specific RNA transcribed from over 120 kb of the KSHV genome in infected cells. One transcript is predicted to encode a small membrane protein; the other is an unusual polyadenylylated RNA that accumulates in the nucleus to high copy number. This pattern of viral gene expression suggests that most infected cells in KS are latently infected, with lytic viral replication likely restricted to a much smaller subpopulation of cells. These findings have implications for the therapeutic utility of currently available antiviral drugs targeted against the lytic replication cycle.
卡波西肉瘤（KS）是HIV感染患者最常见的肿瘤，在一些HIV阴性人群中也有发现。最近，在HIV阳性和HIV阴性患者的KS组织中均鉴定出一种新型疱疹病毒的DNA序列，该病毒被称为KS相关疱疹病毒（KSHV）或人类疱疹病毒8型（HHV-8）；这种病毒的感染被认为是该肿瘤病因或发病机制中的一个可能因素。在此，我们研究了KS中KSHV/HHV-8基因的表达模式，发现其表达受到高度限制。我们鉴定并表征了两种小转录本，它们代表了受感染细胞中从超过120kb的KSHV基因组转录而来的大部分病毒特异性RNA。一种转录本预计编码一种小膜蛋白；另一种是异常的多聚腺苷酸化RNA，在细胞核中大量积累。这种病毒基因表达模式表明，KS中的大多数受感染细胞处于潜伏感染状态，而裂解性病毒复制可能仅限于一小部分细胞亚群。这些发现对目前针对裂解复制周期的抗病毒药物的治疗效用具有启示意义。
