Bruce A Gregory, Bakke Angela M, Bielefeldt-Ohmann Helle, Ryan Jonathan T, Thouless Margaret E, Tsai Che-Chung, Rose Timothy M
Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA.
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
J Gen Virol. 2006 Dec;87(Pt 12):3529-3538. doi: 10.1099/vir.0.82339-0.
Two distinct lineages of rhadinoviruses related to Kaposi's sarcoma (KS)-associated herpesvirus (KSHV; Human herpesvirus 8), the causative agent of KS, have been identified. In macaques, the RV1 lineage is represented by retroperitoneal fibromatosis (RF) herpesvirus (RFHV), the homologue of KSHV, whilst the RV2 lineage is represented by rhesus rhadinovirus (RRV), a more distantly related virus. Real-time quantitative PCR was used to estimate the loads of RV1 and RV2 rhadinoviruses in simian acquired immunodeficiency syndrome-associated RF (SAIDS-RF), a neoplasm of macaques with similarities to AIDS-associated KS. Both RV1 and RV2 rhadinoviruses were detected in macaques with RF. The RV1 loads were 220- to 4300-fold higher in RF tumours than in spleen, showing a strong tumour association (mean loads of 1 800 000 vs 2900 copies per 10(6) cells in tumours and spleen, respectively). In contrast, RV2 loads in the RF tumours were 100-fold lower than RV1 loads and showed similar levels in tumours and spleen (mean loads of 16 000 vs 24 000 copies per 10(6) cells, respectively). Immunostaining with antibodies reactive against RFHV ORF73 latency-associated nuclear antigen (LANA) showed intense nuclear staining of the spindleoid RF tumour cells. Correlation of viral load and the number of LANA-positive cells indicated that RF tumour cells contained multiple copies of the RFHV genome per cell. This pattern of infectivity is similar to that seen in KS tumours latently infected with KSHV. Our study demonstrates similarities in the biology of KSHV and RFHV and supports a role for RFHV in the aetiology of SAIDS-RF.
与卡波西肉瘤（KS）相关疱疹病毒（KSHV；人类疱疹病毒8型）相关的两种不同的疱疹病毒谱系已被确定，KSHV是KS的病原体。在猕猴中，RV1谱系由腹膜后纤维瘤病（RF）疱疹病毒（RFHV）代表，它是KSHV的同源物，而RV2谱系由恒河猴疱疹病毒（RRV）代表，这是一种亲缘关系较远的病毒。实时定量PCR用于估计RV1和RV2疱疹病毒在猿猴获得性免疫缺陷综合征相关RF（SAIDS-RF）中的载量，SAIDS-RF是一种与艾滋病相关KS相似的猕猴肿瘤。在患有RF的猕猴中检测到了RV1和RV2疱疹病毒。RF肿瘤中RV1的载量比脾脏中的高220至4300倍，显示出与肿瘤的强烈关联（肿瘤和脾脏中每10^6个细胞的平均载量分别为1800000和2900拷贝）。相比之下，RF肿瘤中RV2的载量比RV1的载量低100倍，并且在肿瘤和脾脏中的水平相似（每10^6个细胞的平均载量分别为16000和24000拷贝）。用针对RFHV ORF73潜伏相关核抗原（LANA）的抗体进行免疫染色显示，梭形RF肿瘤细胞有强烈的核染色。病毒载量与LANA阳性细胞数量的相关性表明，RF肿瘤细胞每个细胞含有多个RFHV基因组拷贝。这种感染模式与在潜伏感染KSHV的KS肿瘤中看到的模式相似。我们的研究证明了KSHV和RFHV生物学特性的相似性，并支持RFHV在SAIDS-RF病因学中的作用。
