The KSHV ORF20 Protein Interacts with the Viral Processivity Factor ORF59 and Promotes Viral Reactivation

Abstract

Kaposi’s Sarcoma-associated herpesvirus (KSHV) is a herpesvirus that induces lifelong infection, and as such, its lytic replication is carefully controlled to allow for efficient dissemination from its long-term reservoir and for the spread of the virus to new hosts. Viral DNA replication involves many host and viral proteins, coordinating both in time and space to successfully progress through the viral life cycle.

Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence

“…However, the expression of OASL during KSHV infection is beneficial to viral replication. Following the deletion of ORF20, the production of new virions and the replication of viral DNA in KSHV-infected cells were significantly reduced compared with those in cells infected with wild-type viruses, suggesting that ORF20 plays a key role in regulating the replication of KSHV ( Hoffman et al, 2021 ). The mechanism involves ORF20 interacting with OASL, leading to an increase in OASL expression and subsequently promoting the replication of KSHV ( Bussey et al, 2018 ).…”

“…Except for channel catfish herpesvirus, UL24 protein is conserved in the whole herpesvirus family ( Davison, 1992 ; Bertrand et al, 2010 ). The proteins encoded by the HCMV UL76, VZV ORF35, KSHV ORF20 and EHV-1 ORF37 genes also belong to the herpesvirus UL24 protein family ( Bateman et al, 2004 ; Ito et al, 2005 ; Kasem et al, 2010 ; Hoffman et al, 2021 ). Except for the HCMV UL76 gene, the UL24 genes and TK genes of other herpesviruses are arranged in a head-to-head manner at the 5′ end ( Figure 1B ; Jacobson et al, 1989 ; Dezélée et al, 1996 ; Shimojima et al, 1997 ; Pearson and Coen, 2002 ; Ito et al, 2005 ; Li et al, 2006 ).…”