Burnside Kellie L, Ryan Jonathan T, Bielefeldt-Ohmann Helle, Gregory Bruce A, Thouless Margaret E, Tsai Che-Chung, Rose Timothy M
Department of Pathobiology, School of Public Health and Community Medicine, HSB Rm F161E, Box 357238, University of Washington, Seattle, WA 98195, USA.
Virology. 2006 Oct 10;354(1):103-15. doi: 10.1016/j.virol.2006.06.022. Epub 2006 Aug 1.
Retroperitoneal fibromatosis herpesvirus (RFHV), the macaque homolog of the human rhadinovirus, Kaposi's sarcoma-associated herpesvirus (KSHV), was first identified in retroperitoneal fibromatosis (RF) tumor lesions of macaques with simian AIDS. We cloned and sequenced the ORF73 latency-associated nuclear antigen (LANA) of RFHVMn from the pig-tailed macaque. RFHVMn LANA is structurally analogous to KSHV ORF73 LANA and contains an N-terminal serine-proline-rich region, a large internal glutamic acidic-rich repeat region and a conserved C-terminal domain. RFHVMn LANA reacts with monoclonal antibodies specific for a glutamic acid-proline dipeptide motif and a glutamic acid-glutamine-rich motif in the KSHV LANA repeat region. Immunohistochemical and immunofluorescence analysis revealed that RFHVMn LANA is a nuclear antigen which is highly expressed in RF spindloid tumor cells. These data suggest that RFHV LANA is an ortholog of KSHV LANA and will function similarly to maintain viral latency and play a role in tumorigenicity in macaques.
腹膜后纤维瘤病疱疹病毒(RFHV)是人类γ疱疹病毒卡波西肉瘤相关疱疹病毒(KSHV)的猕猴同源物,最初是在患有猴艾滋病的猕猴的腹膜后纤维瘤病(RF)肿瘤病变中发现的。我们从猪尾猕猴中克隆并测序了RFHVMn的ORF73潜伏相关核抗原(LANA)。RFHVMn LANA在结构上类似于KSHV ORF73 LANA,包含一个富含丝氨酸 - 脯氨酸的N端区域、一个大的富含谷氨酸的内部重复区域和一个保守的C端结构域。RFHVMn LANA与针对KSHV LANA重复区域中谷氨酸 - 脯氨酸二肽基序和富含谷氨酸 - 谷氨酰胺基序的单克隆抗体发生反应。免疫组织化学和免疫荧光分析表明,RFHVMn LANA是一种核抗原,在RF梭形肿瘤细胞中高度表达。这些数据表明,RFHV LANA是KSHV LANA的直系同源物,在维持病毒潜伏以及在猕猴的肿瘤发生中发挥作用方面功能类似。