Abortive Lytic Reactivation of KSHV in CBF1/CSL Deficient Human B Cell Lines

• DOI: 10.1371/journal.ppat.1003336
• Publication Date: 2013-05-16T21:22:28Z
• Authors: Barbara A. Scholz; Marie L. Harth-He...; Georg Malterer; Juergen Haas; Joachim Ellwart; Thomas F. Schulz; Bettina Kempkes
• Keywords: Lytic cycle

Since Kaposi's sarcoma associated herpesvirus (KSHV) establishes a persistent infection in human B cells, cells are critical compartment for viral pathogenesis. RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular binding factors including CBF1/CSL as adaptors. In addition, LANA1 vIRF4 known modulate RTA activity. To analyze contribution reactivation we have successfully infected DG75 knock-out cell lines with recombinant KSHV.219 selected maintenance by selective medium. Both maintained virus irrespective their status. Viral could be initiated both but genome was attenuated deficient lines, which also failed produce detectable levels infectious virus. Induction immediate early, early late genes impaired at multiple stages process restored wild-type reintroduction CBF1/CSL. identify additional target genes, controlled CBF1/CSL, analyzed promoters subset genes. We show that induction ORF29a ORF65 is strongly enhanced Orthologs other herpesviruses part terminase complex required packaging. encodes small capsid protein essential shell assembly. Our study demonstrates first time absence severely all does not lead virion production. Thus, acts global hub used coordinate lytic cascade.