The most recently discovered herpesvirus, Kaposi’s sarcoma herpesvirus (KSHV) is known to cause three human cancers. Effective antiviral therapeutics are needed for the treatment of KSHV.
KSHV Viral DNA Replication
Viral DNA replication and the KSHV DNA replication proteins are essential to successful viral replication. Our focus is characterizing the functions and molecular interactions of the core KSHV DNA replication proteins in order to develop potential therapeutic strategies against KSHV infection. Herpesviruses encode their own DNA replication machinery.
Essential KSHV DNA replication proteins: DNA polymerase (ORF9), polymerase accessory factor (ORF59), helicase (ORF44), primase (ORF56), primase associated factor (ORF40/41), and single-stranded DNA binding protein (ORF6).
KSHV, like all herpesviruses establishes a lifelong infection. Viral infections is divided into two phases of its lifecycle, lytic (active) and latent (dormant). After an initial lytic burst of primary infection, virally infected cells transition into the latent phase. During latency, the linear 165kb double stranded DNA viral genome forms an episome (circular double stranded DNA structure) chromatinized with host cell histones and tethered to the host cell chromosomes. Gene expression during latency is restricted to a small subset of viral genes and miRNAs in order to maintain viral episome, avoid immune surveillance and promote infected cell survival. Over the course of infection, viral reactivation, the shift from latency to an active infection, occurs sporadically. Spontaneous lytic reactivation in a KSHV infected individual is necessary for persistent viral infection, disease and oncogenesis.