Kaposi's sarcoma-associated herpesvirus and innate immunity

After entry via endocytosis, KSHV stimulates TLR3, which leads to upregulation of downstream cytokines such as CXCL-10 and IFN-β1 in monocytes, while KSHV can downregulate the expression of TLR4 after endothelial cell infection. KSHV vGPCR along with vIRF1 are responsible for this TLR4 inhibition. The KSHV ORF45 IE gene inhibits IRF-7, while KSHV RTA targets IRF for degradation via ubiquitination. vIRF-1 binds CBP/p300, inhibiting the transcription of cellular IRFs and the IFN response. vIRF-3 blocks the activation of the IFN response by blocking IRF-7 binding to IFN promoters. vIRF-2 also blocks the IFN response via inhibiting the transcription function of cellular IRFs. Finally, in the context of latency, TLR7/8 stimulation with poly-(U)ridine or vesicular stomatitis virus, leads to reactivation of latent KSHV and infectious virion production. IFN: Interferon; IRF: Interferon regulatory factor; KSHV: Kaposi's sarcoma-associated herpesvirus; TLR: Toll-like receptor; vGPCR: Viral G protein-coupled receptor; vIRF: Viral interferon regulatory factor; VSV: Vesicular stomatitis virus.

Publication

Kaposi's sarcoma-associated herpesvirus and innate immunity. () John A West, et al. Future Virol. ;5(2):185-196. Figure: F1. Homo sapiens

Disease mentions