A map of binary SARS-CoV-2 protein interactions implicates host immune regulation and ubiquitination
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Abstract
Key steps in viral propagation, immune suppression, and pathology are mediated by direct, binary, physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary interactions between viral and host proteins, complementing previous co-complex association maps by conveying more direct mechanistic understanding and potentially enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, and confirming high quality of these interactions via a calibrated orthogonal assay. Host proteins interacting with SARS-CoV-2 proteins are enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The binary virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.
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SciScore for 10.1101/2021.03.15.433877: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations and further directions: All protein interaction assays have limitations intrinsic to each method. Y2H assays are limited by the fact that proteins are exogenously expressed with functional assay tags and targeted to …
SciScore for 10.1101/2021.03.15.433877: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations and further directions: All protein interaction assays have limitations intrinsic to each method. Y2H assays are limited by the fact that proteins are exogenously expressed with functional assay tags and targeted to the nucleus. The heterologous nature of the assays and circumvention of physiological transcriptional regulation are limitations, but also a benefit in that they enable detection of interactions that might otherwise be missed. For example, screens that rely on the expression of one or both partners in a given cell line and growth condition might miss interactions for proteins that are not expressed in that cell line, even where these interactions are important in other tissues (Hikmet et al., 2020). Despite these limitations, it has been demonstrated repeatedly that Y2H systems, when quality controlled by orthogonal validation with empirically benchmarked assays as done here, yield high-quality interactions that enable important and robust biological insights (Altmann et al., 2020; Choi et al., 2019; Luck et al., 2020; Rolland et al., 2014; Yu et al., 2008). A known issue with every carefully conducted interaction assay is that true interactions can be missed, with only 20-40% of reference interactions being detectable by any single assay (Braun et al., 2009; Choi et al., 2019; Luck et al., 2020; Yu et al., 2008). This was a major motivation for applying complementary parallel approaches in this study. Future efforts might expand the barcoded ORFeome a...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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