Page 12 - O. Microbiology

[O. Microbiology-14]

Viral processivity factor (PF-8) hijacks CHFR, a cellular E3-

ubiquitin ligase and degrades PARP-1 to promote lytic

replication of Kaposi’s sarcoma-associated herpesvirus

Woo-Chang Chung¹, Seungrae Lee¹, Yejin Kim¹, Jong Bok Seo¹, Moon Jung Song¹

¹Virus-Host Interactions Laboratory, College of Life Sciences and Biotechnology, Korea University, Seoul 02841,

Republic of Korea, ²2Metabolome Analysis Team, Korea Basic Science Institute, Seoul 02841, Republic of Korea

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with tumorigenesis, while its reactivation and lytic
replication are important for the virus propagation and transmission. Poly (ADP-ribose) polymerase-1 (PARP-1) is

involved in key cellular activities such as DNA damage responses, gene transcription and apoptosis by transferring
an (ADP-ribose) moiety (PARylation) to target protein. In KSHV infection, PARP-1 interacts with and PARylates RTA,

a key switch molecule of the virus lytic replication, inhibiting KSHV replication. Here, we identified that KSHV
downregulated PARP-1 upon reactivation. Among viral lytic proteins, ORF59 encoding viral processivity factor, PF-8,

interacted with and degraded PARP-1 in a proteasome-ubiquitin dependent manner. PF-8-mediated PARP-1
degradation enhanced the transactivation activity of RTA and promoted lytic replication. Among cellular E3 ubiquitin-

ligases ubiquitinating PARP-1, PF-8 employed CHFR to degrade PARP-1. Studies with knockdown or overexpression
of CHFR showed that CHFR was important for PF-8-induced PARP-1 degradation and enhancement of the RTA

activity. Taken together, our results demonstrate a viral mechanism of PF-8 hijacking a cellular E3-ligase to overcome
PARP-1 suppression, thereby facilitating KSHV replication.