Molecular profiling of immune cell-enriched Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacting protein USP13

Abstract

Aims Coronavirus disease 2019 (COVID-19), which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a major health concern worldwide. Due to the lack of specific medication and vaccination, drug-repurposing attempts has emerged as a promising approach and identified several human proteins interacting with the virus. This study aims to provide a comprehensive molecular profiling of the immune cell-enriched SARS-CoV-2 interacting protein USP13. Materials and methods The list of immune cell-enriched proteins interacting with SARS-CoV-2 was retrieved from The Human Protein Atlas. Genomic alterations were identified using cBioPortal. Survival analysis was performed via Kaplan-Meier Plotter. Analyses of protein expression and tumor infiltration levels were carried out by TIMER. Key findings 14 human proteins that interact with SARS-CoV-2 were enriched in immune cells. Among these proteins, USP13 had the highest frequency of genomic alterations. Higher USP13 levels were correlated with improved survival in breast and lung cancers, while resulting in poor prognosis in ovarian and gastric cancers. Furthermore, copy number variations of USP13 significantly affected the infiltration levels of distinct subtypes of immune cells in head & neck, lung, ovarian and stomach cancers. Although our results suggested a tumor suppressor role for USP13 in lung cancer, in other cancers, its role seemed to be context-dependent. Significance It is critical to identify and characterize human proteins that interact with SARS-CoV-2 in order to have a better understanding of the disease and to develop better therapies/vaccines. Here, we provided a comprehensive molecular profiling the immune cell-enriched SARS-CoV-2 interacting protein USP13, which will be useful for future studies.

Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection

“…However, SARS-CoV-2 can hijack the host's deubiquitinating enzyme system to counteract the antiviral response. For example, as a protein that interacts with SARS-CoV-2, ubiquitin-specific peptidase 13 (USP13) displays a considerably high incidence of genomic alterations within immune cells of SARS-CoV-2 patients (Süt, 2020). Although USP13 assumes an antiviral role during the pathogenesis of SARS-CoV-2 (Ravindran et al, 2022), some contend that in specific scenarios, USP13 not only fails to impart antiviral effects but instead stimulates viral invasion.…”

Epigenetic Regulation Mechanisms in Viral Infections: A Special Focus on COVID-19

“…Viral proteins Nsp13 and Orf10 interact with ubiquitin specific peptidase USP13 and the components of the Cullin-RING E3 ubiquitin ligase complex, respectively. USP13 has previously been attributed significant immune response-related roles in interferon-induced signaling by STAT1 targeting and deubiquitination [97] and increased immune cell infiltration in several types of cancers [98]. Interestingly, USP13 antagonizes antiviral response via ubiquitination of STING, an important effector of innate immune signaling in response to viral infections [99].…”

Research Progress for Targeting Deubiquitinases in Gastric Cancers

“…Snail phosphorylation at four Ser sites (Ser-107, 111, 115, and 119) causes cytoplasmic localization, whereas phosphorylation at two Ser sites (Ser-96 and 100) promotes ubiquitination and degradation by β-TrCP [ 136 ]. USP13, USP29, and USP37 were reported to promote the metastasis of GC by deubiquitinating and stabilizing Snail [ 35 , 36 , 54 , 59 ]. In addition, the upstream events of USP29 and USP37 are relevant for Snail regulation.…”