Molecular mimicry of host short linear motif-mediated interactions utilised by viruses for entry

Abstract

Viruses are obligate intracellular parasites that depend on host cellular machinery for performing even basic biological functions. One of the many ways they achieve this is through molecular mimicry, wherein the virus mimics a host sequence or structure, thereby being able to hijack the host's physiological interactions for its pathogenesis. Such adaptations are specific recognitions that often confer tissue and species-specific tropisms to the virus, and enable the virus to utilise previously existing host signalling networks, which ultimately aid in further steps of viral infection, such as entry, immune evasion and spread. A common form of sequence mimicry utilises short linear motifs (SLiMs). SLiMs are short-peptide sequences that mediate transient interactions and are major elements in host protein interaction networks. This work is aimed at providing a comprehensive review of current literature of some well-characterised SLiMs that play a role in the attachment and entry of viruses into host cells, which mimic physiological receptor-ligand interactions already present in the host. Considering recent trends in emerging diseases, further research on such motifs involved in viral entry can help in the discovery of previously unknown cellular receptors utilised by viruses, as well as help in the designing of targeted therapeutics such as vaccines or inhibitors directed towards these interactions.

Novel Insights into Phytoplasma Effectors

“…Pathogens and hosts are constantly coevolving, and SLiMs/ELMs are becoming increasingly studied in pathogens, as these mimic critical host motifs, allowing mimicry peptides (mimitopes) to sabotage key host processes [117,[127][128][129][130][131]. Since these SLiMs are abundant and critically important in pathogenesis, they are now being studied as novel drug targets [65,103], either to screen for novel molecules [118], or by docking-based peptide design that disrupts mimitope-host target interaction [132][133][134].…”

Prediction of motif-mediated viral mimicry through the integration of host–pathogen interactions

“…These interactions involve hijacking cellular components and countering host defences, posing challenges in the timely identification of targeted viral and host proteins (Rampersad and Tennant 2018 ; Sumbria et al 2020 ; Bhutkar et al 2022 ). Molecular mimicry by viruses, particularly through Short Linear Motifs (SLiMs) (Glavina et al 2018 ; Venkatakrishnan et al 2020 ; Idrees and Paudel 2023a ; Idrees et al 2023 ), has become an intriguing area of study, allowing viruses to effectively replicate, colonise host cells, and evade detection (Benedict et al 2002 ; Finlay and McFadden 2006 ; Hraber et al 2020 ; Goswami et al 2023 ; Mihalič et al 2023 ). In recent years, different computational studies have been conducted to study the host–pathogen interactions (Dyer et al 2008 ).…”