the rbp-jκ binding sites within the rta promoter regulate kshv latent infection and cell proliferation中的rbp-jκ结合位点等启动子调控kshv潜伏性感染和细胞增殖.pdfVIP

The RBP-Jk Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation 1 2 1 1 1 1 Jie Lu , Subhash C. Verma , Qiliang Cai , Abhik Saha , Richard Kuo Dzeng , Erle S. Robertson * 1 Department of Microbiology and Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Microbiology and Immunology, School of Medicine, University of Nevada, Reno, Nevada, United States of America Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is tightly linked to at least two lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). However, the development of KSHV-mediated lymphoproliferative disease is not fully understood. Here, we generated two recombinant KSHV viruses deleted for the first RBP-Jk binding site (RTA1st) and all three RBP-Jk binding sites (RTAall) within the RTA promoter. Our results showed that RTA1st and RTAall recombinant viruses possess increased viral latency and a decreased capability for lytic replication in HEK 293 cells, enhancing colony formation and proliferation of infected cells. Furthermore, recombinant RTA1st and RTAall viruses showed greater infectivity in human peripheral blood mononuclear cells (PBMCs) relative to wt KSHV. Interestingly, KSHV BAC36 wt, RTA1st and RTAall recombinant viruses infected both T and B cells and all three viruses efficiently infected T and B cells in a time-dependent manner early after infection. Also, the capability of both RTA1st and RTAall recombinant viruses to infect CD19+ B cells was significantly enhanced