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. 2025 Apr 13;26(8):3674.
doi: 10.3390/ijms26083674.

Predicting Motif-Mediated Interactions Based on Viral Genomic Composition

Sobia Idrees  1   2 , Keshav Raj Paudel  2 , Mithila Banik  3 , Newton Suwal  4 , Rajan Thapa  5 , Saroj Bashyal  4
Affiliations

Predicting Motif-Mediated Interactions Based on Viral Genomic Composition

Sobia Idrees et al. Int J Mol Sci. .

Abstract

Viruses manipulate host cellular machinery to propagate their life cycle, with one key strategy being the mimicry of short linear motifs (SLiMs) found in host proteins. While databases continue to expand with virus-host protein-protein interaction (vhPPI) data, accurately predicting viral mimicry remains challenging due to the inherent degeneracy of SLiMs. In this study, we investigate how viral genomic composition influences motif mimicry and the mechanisms through which viruses hijack host cellular functions. We assessed domain-motif interaction (DMI) enrichment differences, and also predicted new DMIs based on known viral motifs with varying stringency levels, using SLiMEnrich v.1.5.1. Our findings reveal that dsDNA viruses capture significantly more known DMIs compared to other viral groups, with dsRNA viruses also exhibiting higher DMI enrichment than ssRNA viruses. Additionally, we identified new vhPPIs mediated via SLiMs, particularly within different viral genomic contexts. Understanding these interactions is vital for elucidating viral strategies to hijack host functions, which could inform the development of targeted antiviral therapies.

Keywords: bioinformatics; short linear motifs; viral mimicry; virus–host interactions.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Protein interactions in PHISTO database categorized based on viral genomic composition, (A) proportion of vhPPIs in each viral genomic category, (B) viral classes in each viral genomic category.
Figure 2
Figure 2
DMI enrichment using different stringencies, (A) normalized number of real DMIs (DMI Real = DMI Obs − DMI Ran). Real DMIs captured by the different viral groups available in PHISTO database over 1000x randomizations using different strategies. Y-axis shows the normalized number of real DMIs, (B) Proportion of interacting proteins, motifs, and domains captured by each viral category using different stringencies.
Figure 3
Figure 3
Biological pathways hijacked by human protein interactors, (A) pathways regulated by human proteins predicted to interact with viral proteins via SLiMs using ELMc-Protein stringency, (B) pathways regulated by human proteins predicted to interact using their domains with viral proteins via SLiMs using ELMc-Domain stringency.
Figure 4
Figure 4
Proportion of known interactions in predicted DMIs from different stringencies.
See this image and copyright information in PMC

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References

    1. Glavina J., Palopoli N., Chemes L.B. Evolution of SLiM-mediated hijack functions in intrinsically disordered viral proteins. Essays Biochem. 2022;66:945–958. doi: 10.1042/EBC20220059. - DOI - PubMed
    1. Tenthorey J.L., Emerman M., Malik H.S. Evolutionary Landscapes of Host-Virus Arms Races. Annu. Rev. Immunol. 2022;40:271–294. doi: 10.1146/annurev-immunol-072621-084422. - DOI - PubMed
    1. Hraber P., O’Maille P.E., Silberfarb A., Davis-Anderson K., Generous N., McMahon B.H., Fair J.M. Resources to Discover and Use Short Linear Motifs in Viral Proteins. Trends Biotechnol. 2020;38:113–127. doi: 10.1016/j.tibtech.2019.07.004. - DOI - PMC - PubMed
    1. Villanueva R.A., Rouille Y., Dubuisson J. Interactions between virus proteins and host cell membranes during the viral life cycle. Int. Rev. Cytol. 2005;245:171–244. doi: 10.1016/S0074-7696(05)45006-8. - DOI - PMC - PubMed
    1. Becerra A., Bucheli V.A., Moreno P.A. Prediction of virus-host protein-protein interactions mediated by short linear motifs. BMC Bioinform. 2017;18:163. doi: 10.1186/s12859-017-1570-7. - DOI - PMC - PubMed

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