Abstract
Most viruses have small genomes that encode proteins needed to perform essential enzymatic functions. Across virus families, primary enzyme functions are under functional constraint; however, secondary functions mediated by exposed protein surfaces that promote interactions with the host proteins may be less constrained. Viruses often form transient interactions with host proteins through conformationally flexible interfaces. Exposed flexible amino acid residues are known to evolve rapidly suggesting that secondary functions may generate diverse interaction potentials between viruses within the same viral family. One mechanism of interaction is viral mimicry through short linear motifs (SLiMs) that act as functional signatures in host proteins. Viral SLiMs display specific patterns of adjacent amino acids that resemble their host SLiMs and may occur by chance numerous times in viral proteins due to mutational and selective processes. Through mimicry of SLiMs in the host cell proteome, viruses can interfere with the protein interaction network of the host and utilize the host-cell machinery to their benefit. The overlap between rapidly evolving protein regions and the location of functionally critical SLiMs suggest that these motifs and their functional potential may be rapidly rewired causing variation in pathogenicity, infectivity, and virulence of related viruses. The following review provides an overview of known viral SLiMs with select examples of their role in the life cycle of a virus, and a discussion of the structural properties of experimentally validated SLiMs highlighting that a large portion of known viral SLiMs are devoid of predicted intrinsic disorder based on the viral SLiMs from the ELM database.
Highlights
Based on prediction of disorder, surface accessibility, and secondary structure, our results suggest that a large portion of the true positive viral short linear motifs (SLiMs) are not disordered but a clear majority are in a coil conformation and an even stronger signal is seen from prediction of surface accessibility
We highlighted the importance of viral mimicry mediated by SLiMs at select steps of the virus life cycle
We showed how specific SLiMs might affect virulence and pathogenicity
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Structural proteins encapsulate the newly formed virus genome inside the host cell and provide the virion its shape. Accessory proteins are mainly regulatory proteins primarily involved in modulating host cell gene expression, inducing apoptosis, or affecting the viral rate of replication [4]. The fitness of RNA viruses depends on their RNA polymerases to replicate the viral genome with low fidelity [7,8]. Through interface mimicry, where a part of a viral protein surface resembles a host protein, the virus can interfere with protein-protein networks of the host protein [9]. Identification of a SLiM from a host species in a viral protein suggests interface mimicry that may disrupt endogenous protein-protein interactions. Many host-virus mimicry-driven interactions are transient [10] and depend on the proteomic context of the host cell. Exogeneous interactions may give rise to complex diversity in virulence, pathogenicity, and transmissibility between different host species, and within the same host species
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call