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Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
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Rapidly evolving viral motifs mostly target biophysically constrained binding pockets of host proteins
1Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Cell Reports
|August 17, 2022
Summary
Viruses exploit host proteins by mimicking cellular motifs, targeting conserved proteins essential for cell function. Host defenses are limited by evolutionary constraints, enabling viral manipulation of cellular pathways.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Host-virus interactions are shaped by evolutionary pressures.
- Understanding the constraints on these interactions is crucial for deciphering infection dynamics.
- Viral mimicry of host motifs is a key strategy for subverting cellular pathways.
Purpose of the Study:
- To investigate the biophysical and regulatory constraints governing the evolution of host-virus interfaces.
- To identify characteristics of host proteins targeted by viral mimicry.
- To differentiate between conserved and rapidly evolving host-virus interfaces.
Main Methods:
- Analysis of viral mimicry motifs and their targeted host proteins.
- Comparison of interface properties between viral-interacting and non-viral-interacting host domains.
- Assessment of host protein conservation, expression, connectivity, and function.
Main Results:
- Viral mimicry motifs preferentially target conserved, widely expressed host proteins with essential regulatory functions.
- Host domains interacting with viral motifs exhibit higher residue conservation and more cellular interactions.
- Rapidly evolving viral-binding host proteins show low interaction diversity and high tissue specificity.
Conclusions:
- Host protein evolution is constrained, limiting its capacity to resist viral mimicry.
- Conserved host proteins are vulnerable to viral subversion due to their essential and interconnected nature.
- Distinct evolutionary trajectories exist for different host-virus interfaces, impacting infection outcomes.
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