Kaposi's sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV establishes a life-long infection in its host and alternates between a latent and lytic infection state. During lytic infection, lytic-related genes are expressed in a temporal manner and categorized as immediate early, early, and late gene transcripts. ORF34 is an early-late gene that interacts with several viral transcription-associated factors, however its physiological importance remains poorly understood. Here, we investigated the role of ORF34 during KSHV infection by generating ORF34-deficient KSHV, using a bacterial artificial chromosome system. Our results reveal that ORF34-deficient KSHV exhibited significantly attenuated late gene expression and viral production but did not affect viral DNA replication. ORF34 interacted with transcription factors ORF18, ORF24, ORF31, and ORF66, and a novel ORF34-interaction partner, ORF23. The C-terminal region of ORF34 was important for interaction with ORF24 and viral production. Our data support a model, in which ORF34 serves as a hub for recruiting a viral transcription complex to ORF24 to promote late viral gene expression.
Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto, 607-8412, Japan.
Mayu
M
Nishimura
Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto, 607-8412, Japan.
Tadashi
T
Watanabe
Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto, 607-8412, Japan.
Syota
S
Yagi
Takahiro
T
Yamanaka
Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto, 607-8412, Japan. fuji2@mb.kyoto-phu.ac.jp.
Masahiro
M
Fujimuro
D000818:Animals; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D055786:Gene Knockout Techniques; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D025941:Protein Interaction Mapping; D014158:Transcription, Genetic; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D017361:Viral Nonstructural Proteins