NDRG1 facilitates lytic replication of Kaposi's sarcoma-associated herpesvirus by maintaining the stability of the KSHV helicase.
PLoS Pathog
; 17(6): e1009645, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-34077484
ABSTRACT
The presumed DNA helicase encoded by ORF44 of Kaposi's sarcoma-associated herpesvirus (KSHV) plays a crucial role in unwinding viral double-stranded DNA and initiating DNA replication during lytic reactivation. However, the regulatory mechanism of KSHV ORF44 has not been fully elucidated. In a previous study, we identified that N-Myc downstream regulated gene 1 (NDRG1), a host scaffold protein, facilitates viral genome replication by interacting with proliferating cell nuclear antigen (PCNA) and the latent viral protein latency-associated nuclear antigen (LANA) during viral latency. In the present study, we further demonstrated that NDRG1 can interact with KSHV ORF44 during viral lytic replication. We also found that the mRNA and protein levels of NDRG1 were significantly increased by KSHV ORF50-encoded replication and transcription activator (RTA). Remarkably, knockdown of NDRG1 greatly decreased the protein level of ORF44 and impaired viral lytic replication. Interestingly, NDRG1 enhanced the stability of ORF44 and inhibited its ubiquitin-proteasome-mediated degradation by reducing the polyubiquitination of the lysine residues at positions 79 and 368 in ORF44. In summary, NDRG1 is a novel binding partner of ORF44 and facilitates viral lytic replication by maintaining the stability of ORF44. This study provides new insight into the mechanisms underlying KSHV lytic replication.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Proteínas Inmediatas-Precoces
/
Proteínas de Ciclo Celular
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Herpesvirus Humano 8
/
Péptidos y Proteínas de Señalización Intracelular
/
Interacciones Huésped-Patógeno
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2021
Tipo del documento:
Article
País de afiliación:
China