Mary Wilson
Well-known member
(In title error: should be ASM (ASM Journal) not AMS)
21 January 2025
https://doi.org/10.1128/jvi.02029-24
Xinglong Qu, Ziqi Zhu, Xinpei Zhou, Xuehan Wu, Xin Liu, Xiaoyu Sun, Jiayue Zhang, Guanyi Du, Runyu Xue, Qianhua Zhang, Wenyan Zhang, Zhaolong Li
ABSTRACT
Respiratory syncytial virus (RSV) infections continue to plague infants, young children, and older individuals worldwide. Since there is no specific treatment for RSV, characterizing the interactions between RSV and host factors remains crucial for the eventual development of robust therapeutic interventions. In our previous study, guanylate binding protein 5 (GBP5) was shown to promote excessive RSV-small hydrophobic (RSV-SH) protein secretion by microvesicles and inhibited viral replication. In this study, using affinity mass spectrometry, keratin (KRT) 9 was identified to be required for GBP5 to trigger RSV-SH transport. Silencing KRT9 expression reduced the antiviral effects of GBP5 and interferon-γ. A direct interaction was detected between KRT9 and GBP5, but not RSV-SH; a GBP5 binding domain was identified on KRT9. Our results suggest that GBP5, as a bridge, interacts with KRT9 and RSV-SH, after which KRT9 triggers RSV-SH transport. The mechanism underlying the interaction between KRT9 and GBP5 explains the inability of the GBP5-C583A and GBP5-△C mutants in inhibiting RSV replication. Conversely, KRT1, KRT5, and KRT6C, which were identified as potential partners of KRT9, did not affect the GBP5 anti-RSV process. Overall, our study provides evidence for KRT9 involvement in host innate immunity for the first time.
https://journals.asm.org/doi/10.1128/jvi.02029-24
21 January 2025
https://doi.org/10.1128/jvi.02029-24
Xinglong Qu, Ziqi Zhu, Xinpei Zhou, Xuehan Wu, Xin Liu, Xiaoyu Sun, Jiayue Zhang, Guanyi Du, Runyu Xue, Qianhua Zhang, Wenyan Zhang, Zhaolong Li
ABSTRACT
Respiratory syncytial virus (RSV) infections continue to plague infants, young children, and older individuals worldwide. Since there is no specific treatment for RSV, characterizing the interactions between RSV and host factors remains crucial for the eventual development of robust therapeutic interventions. In our previous study, guanylate binding protein 5 (GBP5) was shown to promote excessive RSV-small hydrophobic (RSV-SH) protein secretion by microvesicles and inhibited viral replication. In this study, using affinity mass spectrometry, keratin (KRT) 9 was identified to be required for GBP5 to trigger RSV-SH transport. Silencing KRT9 expression reduced the antiviral effects of GBP5 and interferon-γ. A direct interaction was detected between KRT9 and GBP5, but not RSV-SH; a GBP5 binding domain was identified on KRT9. Our results suggest that GBP5, as a bridge, interacts with KRT9 and RSV-SH, after which KRT9 triggers RSV-SH transport. The mechanism underlying the interaction between KRT9 and GBP5 explains the inability of the GBP5-C583A and GBP5-△C mutants in inhibiting RSV replication. Conversely, KRT1, KRT5, and KRT6C, which were identified as potential partners of KRT9, did not affect the GBP5 anti-RSV process. Overall, our study provides evidence for KRT9 involvement in host innate immunity for the first time.
https://journals.asm.org/doi/10.1128/jvi.02029-24