Human Herpesvirus 6B U26 Inhibits the Activation of the RLR/MAVS Signaling Pathway
| Autor: | Linyun Li, Xuefeng Jiang, Xiangjun Chen, Huaming Tang, Yuhang Wang, Lily Wang, Peipei Li, Shuhua Chen, Jinfeng Guo, Tian Tang, Junli Jia, Benshun Hu, Yiqun Wen, Garbarino Emanuela, Kun Yao |
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| Rok vydání: | 2021 |
| Předmět: |
Herpesvirus 6
Human viruses Mitochondrion Biology Microbiology Virus Viral Proteins 03 medical and health sciences 0302 clinical medicine U26 Virology Humans Receptors Immunologic Gene Adaptor Proteins Signal Transducing 030304 developmental biology Mitochondrial antiviral-signaling protein 0303 health sciences Gene knockdown Innate immune system Host Microbial Interactions virus diseases RNA biochemical phenomena metabolism and nutrition QR1-502 Immunity Innate Cell biology RLR/MAVS signaling pathway HEK293 Cells Gene Knockdown Techniques Host-Pathogen Interactions DEAD Box Protein 58 Signal transduction HHV-6B 030217 neurology & neurosurgery Research Article Protein Binding Signal Transduction |
| Zdroj: | mBio mBio, Vol 12, Iss 1 (2021) |
| ISSN: | 2150-7511 2161-2129 |
| DOI: | 10.1128/mbio.03505-20 |
| Popis: | U26 is one of the roseolovirus unique genes with unknown function. Human herpesvirus 6B (HHV-6B) pU26 is predicted to be an 8-transmembrane protein containing a mitochondrion location signal. Here, we analyzed U26 function during HHV-6B infection and find that (i) HHV-6B U26 is expressed at a very early stage during HHV-6B infection, and knockdown of it results in a significant decrease of HHV-6B progeny virus production; (ii) U26 inhibits the activation of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)/mitochondrial antiviral signaling protein (MAVS) signaling pathway, an important anti-HHV-6B infection innate immune response, by targeting MAVS protein for degradation; and (iii) a portion of U26 locates to the mitochondria, which could affect the mitochondrial membrane potential and finally leads to MAVS degradation. These findings indicate that HHV-6B U26 is a novel antagonistic viral factor against host innate antiviral immunity.IMPORTANCE HHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help develop a new therapy against HHV-6B infection. |
| Databáze: | OpenAIRE |
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