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Review
, 87 (17), 9398-410

Distinct Roles of Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral Interferon Regulatory Factors in Inflammatory Response and Cancer

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Review

Distinct Roles of Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral Interferon Regulatory Factors in Inflammatory Response and Cancer

Petra Baresova et al. J Virol.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Similar to other herpesviruses, KSHV has two life cycles, latency and lytic replication. In latency, the KSHV genome persists as a circular episome in the nucleus of the host cell and only a few viral genes are expressed. In this review, we focus on oncogenic, antiapoptotic, and immunomodulating properties of KSHV-encoded homologues of cellular interferon regulatory factors (IRFs)--viral IRF1 (vIRF1) to vIRF4--and their possible role in the KSHV-mediated antiviral response, apoptosis, and oncogenicity.

Figures

Fig 1
Fig 1
Homology and gene arrangement of KSHV-encoded vIRFs. (A) Gene arrangement of the vIRF locus in the KSHV genome. Open reading frames encoding vIRFs are located between ORF57 and ORF58 (83 to 95 kb). (B) Homology of vIRFs with cellular IRFs and rhesus macaque rhadinovirus (RRV)-encoded vIRFs. The degree of homology/identity was determined by BLASTp analysis using the UniProtKB database (http://uniprot.org).
Fig 2
Fig 2
Schematic illustration of multiple immunomodulatory functions of KSHV within infected cells. Viral infection leads to activation of type I and II interferon signaling. Viral IRFs inhibit alpha, beta, and gamma interferon transcription, NF-κB activation, and MHC-I and II gene expression. P, phosphorus; TBK1, TANK-binding kinase 1.
Fig 3
Fig 3
Schematic illustration of oncogenic and antiapoptotic functions of KSHV. Virus infection and DNA damage activate p53 and proapoptotic signaling. Viral IRFs effectively inhibit p53-mediated transcription and protein stability and function. vIRFs also regulate the proapoptotic pathway via inhibition of effector proteins, including GRIM19, 14-3-3, and FOXO3a, as well as Bim and Bid function. In addition, vIRF-3 activates c-Myc- and HIF-1α-mediated transcription. Other cellular pathways regulated by vIRFs include TGF-β, Notch, and CD95 signaling. Ub, ubiquitin.

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