mutual inhibition between kaposis sarcoma-associated herpesvirus and epstein-barr virus lytic replication initiators in dually-infected primary effusion lymphoma卡波济氏肉瘤相关疱疹病毒之间的相互抑制,巴尔病毒裂解复制在病人的主要发起者积液淋巴瘤.pdfVIP

Mutual Inhibition between Kaposi’s Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Lytic Replication Initiators in Dually-Infected Primary Effusion Lymphoma 1. 1. 2 1,2 Yanjun Jiang , Dongsheng Xu , Yong Zhao , Luwen Zhang * 1 Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, United States of America, 2 School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America Abstract Background: Both Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are members of the human gamma herpesvirus family: each is associated with various human cancers. The majority of AIDS-associated primary effusion lymphoma (PEL) are co-infected with both KSHV and EBV. Dually-infected PELs selectively switch from latency to lytic replication of either KSHV or EBV in response to chemical stimuli. KSHV replication and transcription activator (K-RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication, while EBV BZLF1 gene product (EBV-Z) is a critical initiator for induction of EBV lytic replication. Methodology/Principal Findings: We show K-RTA and EBV-Z are co-localized and physically interact with each other in dually-infected PELs. K-RTA inhibits the EBV lytic replication by nullifying EBV-Z-mediated EBV lytic gene activation. EBV-Z inhibits KSHV lytic gene expression by blocking K-RTA-mediated transactivations. The physical interaction between K-RTA and EBV-Z are required for the mutual inhibition of the two molecules. The leucine heptapeptide repeat (LR) region in K-RTA and leucine zipper region in EBV-Z are involved in the physical interactions of the two molecules. Finally, initiation of KSHV lytic gene expres