Dataset Information

SARS-CoV-2 variants evolve convergent strategies to remodel the host response: Infection proteomics

ABSTRACT: We sought to compare differences in the human cellular response to distinct SARS-CoV-2 variants of concern. Here, we infected Calu-3 lung epithelial cells with each of the SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) compared to two early-lineage controls (VIC and IC19). We performed global abundance proteomics and phosphoproteomics at 10, 24, and, for certain samples, 48 hours post infection to comprehensively characterize the host response to infection.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Exploris 480

ORGANISM(S): Severe Acute Respiratory Syndrome Coronavirus 2

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Covid-19

SUBMITTER: Mehdi Bouhaddou

LAB HEAD: Nevan J

PROVIDER: PXD036968 | Pride | 2024-02-16

REPOSITORIES: Pride

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SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

Bouhaddou Mehdi M Reuschl Ann-Kathrin AK Polacco Benjamin J BJ Thorne Lucy G LG Ummadi Manisha R MR Ye Chengjin C Rosales Romel R Pelin Adrian A Batra Jyoti J Jang Gwendolyn M GM Xu Jiewei J Moen Jack M JM Richards Alicia L AL Zhou Yuan Y Harjai Bhavya B Stevenson Erica E Rojc Ajda A Ragazzini Roberta R Whelan Matthew V X MVX Furnon Wilhelm W De Lorenzo Giuditta G Cowton Vanessa V Syed Abdullah M AM Ciling Alison A Deutsch Noa N Pirak Daniel D Dowgier Giulia G Mesner Dejan D Turner Jane L JL McGovern Briana L BL Rodriguez M Luis ML Leiva-Rebollo Rocio R Dunham Alistair S AS Zhong Xiaofang X Eckhardt Manon M Fossati Andrea A Liotta Nicholas F NF Kehrer Thomas T Cupic Anastasija A Rutkowska Magdalena M Mena Ignacio I Aslam Sadaf S Hoffert Alyssa A Foussard Helene H Olwal Charles Ochieng' CO Huang Weiqing W Zwaka Thomas T Pham John J Lyons Molly M Donohue Laura L Griffin Aliesha A Nugent Rebecca R Holden Kevin K Deans Robert R Aviles Pablo P Lopez-Martin Jose A JA Jimeno Jose M JM Obernier Kirsten K Fabius Jacqueline M JM Soucheray Margaret M Hüttenhain Ruth R Jungreis Irwin I Kellis Manolis M Echeverria Ignacia I Verba Kliment K Bonfanti Paola P Beltrao Pedro P Sharan Roded R Doudna Jennifer A JA Martinez-Sobrido Luis L Patel Arvind H AH Palmarini Massimo M Miorin Lisa L White Kris K Swaney Danielle L DL Garcia-Sastre Adolfo A Jolly Clare C Zuliani-Alvarez Lorena L Towers Greg J GJ Krogan Nevan J NJ

Cell 20230921 21

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately conv ...[more]

PMID: 37738970

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Project description:The Wiskott-Aldrich Syndrome Protein (WASP) family is known for its participation in cytoskeleton reorganization (Marchand et al., 2001 and Jia et al., 2010). In 2007, the human subtelomeric MGC52000 genes were renamed as Wiskott-Aldrich Syndrome Protein and SCAR Homolog (WASH). Human WASH proteins are part of the WASP protein family and colocalize with actin in cells and promote Arp2/3-dependent actin polymerization in vitro (Linardopoulou et al., 2007). WASH multiprotein complex consists of seven subunits: notable to mention Strumpelin and Was Protein Family Homolog (WASH)-interacting protein (SWIP), which is encoded by KIAA1033/WASHC4 gene, FAM21 and Arp2/3. The Arp2/3 dependent actin polymerization from G-actin to F-actin is an important step in regulation of the cytoskeleton, enabling multiple endosomal transport processes (Kelleher et al., 1995 and Derivery et al., 2010). Linardopoulou and colleagues have also shown in an animal model (Drosophila), that the single WASH ortholog is essential for viability (Linardopoulou et al., 2007), strengthening the concept, that WASHC4 plays a crucial role in muscle cell integrity and function. A link between autosomal recessive intellectual disability (ARID) and mutations in the KIAA1033/WASHC4 gene was first recognized in 2011 by Ropers and colleagues. Very recently, Assoum and colleagues reported three additional patients (from two unrelated families) with syndromic ID. Two of them being sisters (8 and 6 years), both presenting with learning disabilities, macrocephaly, dysmorphic features, skeletal anomalies and subependymal heterotopic nodules due to a compound heterozygous mutation of the KIAA1033/WASHC4 gene (p.[Gln442*] and p.[Asp1048Gly]). In this study, we precisely describe the clinical phenotype of the two siblings and provide additional information (histological and proteomic data) derived from the muscle biopsy of the elder sibling to confirm the pathogenicity of the reported variant and establish the function of WASHC4 as relevant for muscle homeostasis. Which, as far as the authors know, has not yet been described in literature.

Dataset Information

SARS-CoV-2 variants evolve convergent strategies to remodel the host response: Infection proteomics

Publications

SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

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