Pellino-1, a therapeutic target for control of SARS-CoV-2 infection and disease severity

Binbin Wang; Hongjie Xia; Bi-Hung Peng; Eun-Jin Choi; Bing Tian; Xuping Xie; Shinji Makino; Xiaoyong Bao; Pei-Yong Shi; Vineet Menachery; Tian Wang

doi:10.1016/j.antiviral.2024.106059

Pellino-1, a therapeutic target for control of SARS-CoV-2 infection and disease severity

Antiviral Res. 2024 Dec 15:106059. doi: 10.1016/j.antiviral.2024.106059. Online ahead of print.

Authors

Binbin Wang¹, Hongjie Xia¹, Bi-Hung Peng², Eun-Jin Choi³, Bing Tian⁴, Xuping Xie⁵, Shinji Makino⁶, Xiaoyong Bao⁷, Pei-Yong Shi⁸, Vineet Menachery⁶, Tian Wang⁹

Affiliations

¹ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA.
² Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, TX, USA.
³ Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX, USA.
⁴ Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
⁵ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Institute for Drug Discovery, University of Texas Medical Branch, Galveston, TX, USA.
⁶ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
⁷ Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
⁸ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
⁹ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: ti1wang@utmb.edu.

PMID: 39689784
DOI: 10.1016/j.antiviral.2024.106059

Abstract

Enhanced expression of Pellino-1 (Peli1), a ubiquitin ligase is known to be associated with COVID-19 susceptibility. The underlying mechanisms are not known. Here, we report that mice deficient in Peli1 (Peli1^-/-) had reduced viral load and attenuated inflammatory immune responses and tissue damage in the lung following SARS-CoV-2 infection. Overexpressing Peli1 in 293T cells increased SARS-CoV-2 infection via promoting virus replication and transcription, without affecting virus attachment and entry into the cells. Smaducin-6 treatment which is known to disrupt Peli1-mediated NF-KB activation, attenuated inflammatory immune responses in human lung epithelial cells as well as in the lung of K18-hACE2 mice following SARS-CoV-2 infection, though it had minimal effects on SARS-CoV-2 infection in human nasal epithelial cells. Overall, our findings suggest that Peli1 contributes to SARS-CoV-2 pathogenesis by promoting virus replication and positively regulating virus-induced inflammatory responses in lung epithelial cells. Peli1 is a therapeutic target to control SARS-CoV-2 -induced disease severity.

Keywords: Peli1; SARS-CoV-2; inflammation; pathogenesis; therapeutic.