Abstract
Viruses deploy genetically encoded strategies to coopt host machinery and support viral replicative cycles. Here, we use protein structure similarity to scan for molecular mimicry, manifested by structural similarity between viral and endogenous host proteins, across thousands of cataloged viruses and hosts spanning broad ecological niches and taxonomic range, including bacteria, plants and fungi, invertebrates, and vertebrates. This survey identified over 6,000,000 instances of structural mimicry; more than 70% of viral mimics cannot be discerned through protein sequence alone. We demonstrate that the manner and degree to which viruses exploit molecular mimicry varies by genome size and nucleic acid type and identify 158 human proteins that are mimicked by coronaviruses, providing clues about cellular processes driving pathogenesis. Our observations point to molecular mimicry as a pervasive strategy employed by viruses and indicate that the protein structure space used by a given virus is dictated by the host proteome.A record of this paper’s transparent peer review process is included in the Supplemental Information.
Highlights
Viruses deploy an array of genetically encoded strategies to coopt host machinery and support viral replicative cycles
Structural alignment of the 92,868 templates with PDB proteins identified 6,083,167 mimicry relationships, involving 88,715 viral proteins and 26,542 host protein structures present in the PDB
In accordance with known phenotypes associated with Dengue virus (DENV; Flaviridae) infection (Chuang et al, 2014; Lin et al, 2011), we find that proteins mimicked by these RNA viruses are enriched for functions and pathways related to blood coagulation and the complement pathway—an observation that is mirrored by protein-protein interactions (PPIs) mediated by proteins encoded by these viruses (Lasso et al, 2019)
Summary
Encoded factors resembling host factors hijack host molecular machines in a phenomenon called molecular mimicry. Lasso et al use 3D protein structural information to identify over 6,000,000 instances of structural mimicry, >70% of which cannot be discerned through protein sequence alone. Their work provides the first systematic analysis of molecular mimicry across the earth’s virome. Highlights d Structural mimicry of host proteins is a pervasive strategy across earth’s virome d Majority of the >6,000,000 cataloged mimics cannot be discerned through sequence d Protein structure space utilized by viruses is dictated by host proteomes d Knowledge of viral mimics provides clues about pathophysiology of COVID-19.
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