Contents - College of Medical and Dental Sciences - University of ...

The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Lytic Replication Abstract 36
APPLICATION OF ACTIVE KINOME COLLECTION FOR IDENTIFICATION OF A
NOVEL KINASE FAMILY INVOLVED IN REACTIVATION OF KSHV
Fang Cheng 1 , Markku Varjosalo 1 , Anne Lehtonen 1 , Magdalena Weidner-Glunde 2 , Päivi J.
Koskinen 3 , Thomas Schulz 2 , Jussi Taipale 1 , and Päivi M. Ojala 1 .
1 Genome-Scale Biology Program, Biomedicum Helsinki & Institute of Biomedicine,
University of Helsinki, Helsinki, Finland, 2 Institute of Virology, Hannover Medical School,
Hannover, 3 Turku Center for Biotechnology, Turku, Finland
Abstract
Infection by KSHV displays two different phases: latent and lytic. During latency, the
viral genome is episomal, with only few viral genes expressed. Upon induction of the lytic
cycle, extensive viral DNA replication and viral gene expression is initiated (viral
reactivation), which leads to production of new viral particles. Host signal-transduction
pathways are involved in the switch between latency and productive infection. By using a
gain-of-function human kinome screen, we identified two new kinases, Pim-1 and -3, to
be involved in KSHV reactivation. Ectopic expression of Pim-1 and Pim-3 Kinases induces
viral lytic replication and production of progeny viruses. Silencing of Pim-1 and Pim-3 by
RNA interference demonstrate that Pim-1 and Pim-3 are required for KSHV lytic
reactivation. By performing experiments in both de novo and naturally infected KSHV cell
models we were able to identify the molecular mechanism for Pim-1/3 induced viral
reactivation. The identification of this novel cellular kinase family regulating the
gammaherpesvirus life cycle will facilitate a deeper understanding of KSHV reactivation
and could represent a potential novel target for therapeutic intervention.
Presenting author Email: cheng.fang@helsinki.fi
61