Deciphering flavivirus–host interactions using quantitative proteomics

Li, Minghua; Ramage, Holly; Cherry, Sara

doi:10.1016/j.coi.2020.06.002

Cited by 7 publications

(6 citation statements)

References 64 publications

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“…Together, these RNA and protein species remodel the cell to facilitate the viral life cycle. We and others have demonstrated the utility of functionally exploring how different virally derived molecules hijack the host, in particular in the context of flaviviruses (Li et al, 2020). For example, mapping physical associations between the host and virus at the level of protein-protein interactions (PPIs) have defined key pathways relevant to infection (Eckhardt et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Flynn

Belk

et al. 2021

Cell

174

199

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Section: Introductionmentioning

confidence: 99%

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Flynn

Belk

et al. 2021

Cell

174

199

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“…Together, these RNA and protein species remodel the cell to facilitate the viral life cycle. We and others have demonstrated the utility of functionally exploring how different virally-derived molecules hijack the host, in particular in the context of flaviviruses ( Li et al, 2020 ). For example, mapping physical associations between the host and virus at the level of protein-protein interactions (PPI) have defined key pathways relevant to infection ( Eckhardt et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Systematic discovery and functional interrogation of SARS-CoV-2 viral RNA-host protein interactions during infection

Flynn

Yasumoto

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a pandemic with growing global mortality. There is an urgent need to understand the molecular pathways required for host infection and anti-viral immunity. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host proteins that bind the SARS-CoV-2 RNA during active infection. Integration of this data with viral ChIRP-MS data from three other positive-sense RNA viruses defined pan-viral and SARS-CoV-2-specific host interactions. Functional interrogation of these factors with a genome-wide CRISPR screen revealed that the vast majority of viral RNA-binding proteins protect the host from virus-induced cell death, and we identified known and novel anti-viral proteins that regulate SARS-CoV-2 pathogenicity. Finally, our RNA-centric approach demonstrated a physical connection between SARS-CoV-2 RNA and host mitochondria, which we validated with functional and electron microscopy data, providing new insights into a more general virus-specific protein logic for mitochondrial interactions. Altogether, these data provide a comprehensive catalogue of SARS-CoV-2 RNA-host protein interactions, which may inform future studies to understand the mechanisms of viral pathogenesis, as well as nominate host pathways that could be targeted for therapeutic benefit.Highlights· ChIRP-MS of SARS-CoV-2 RNA identifies a comprehensive viral RNA-host protein interaction network during infection across two species· Comparison to RNA-protein interaction networks with Zika virus, dengue virus, and rhinovirus identify SARS-CoV-2-specific and pan-viral RNA protein complexes and highlights distinct intracellular trafficking pathways· Intersection of ChIRP-MS and genome-wide CRISPR screens identify novel SARS-CoV-2-binding proteins with pro- and anti-viral function· Viral RNA-RNA and RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection

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“…A recent review describes several flavivirus host factors and pathways identified in large-scale AP-MS screens [ 13 • ]. Here we highlight select host factors identified in recent screens performed in human cells with known roles in autophagy.…”

Section: Low-biased Approaches To Identify Flavivirus Host Factorsmentioning

confidence: 99%

Flavivirus–host interactions: an expanding network of proviral and antiviral factors

Schneider

Hoffmann

2022

Current Opinion in Virology

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Flaviviruses are zoonotic pathogens transmitted by the bite of infected mosquitos and ticks and represent a constant burden to human health. Here we review recent literature aimed at uncovering how flaviviruses interact with the cells that they infect. A better understanding of these interactions may ultimately lead to novel therapeutic targets. We highlight several studies that employed low-biased methods to discover new protein–protein, protein–RNA, and genetic interactions, and spotlight recent work characterizing the host protein, TMEM41B, which has been shown to be critical for infection by diverse flaviviruses and coronaviruses.

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Deciphering flavivirus–host interactions using quantitative proteomics

Cited by 7 publications

References 64 publications

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Systematic discovery and functional interrogation of SARS-CoV-2 viral RNA-host protein interactions during infection

Flavivirus–host interactions: an expanding network of proviral and antiviral factors

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