Viral infection and human disease--insights from minimotifs
Krishna Kadaveru1, Jay Vyas, Martin R Schiller
1University of Connecticut Health Center, Department of Molecular, Microbial, and Structural Biology, Biological Systems Modeling Group, 263 Farmington Ave., Farmington, CT, 06030-3305, USA.
Abstract:
Short functional peptide motifs cooperate in many molecular functions including protein interactions, protein trafficking, and posttranslational modifications. Viruses exploit these motifs as a principal mechanism for hijacking cells and many motifs are necessary for the viral life-cycle. A virus can accommodate many short motifs in its small genome size providing a plethora of ways for the virus to acquire host molecular machinery. Host enzymes that act on motifs such as kinases, proteases, and lipidation enzymes, as well as protein interaction domains, are commonly mutated in human disease, suggesting that the short peptide motif targets of these enzymes may also be mutated in disease; however, this is not observed. How can we explain why viruses have evolved to be so dependent on motifs, yet these motifs, in general do not seem to be as necessary for human viability? We propose that short motifs are used at the system level. This system architecture allows viruses to exploit a motif, whereas the viability of the host is not affected by mutation of a single motif.
Insights
Viruses heavily rely on short functional peptide motifs to hijack host cells. Host cells, however, are resilient to single motif mutations due to a system-level architecture, explaining viral dependence and host viability.
Area of Science:
- Molecular biology
- Virology
- Systems biology
Background:
- Short functional peptide motifs are crucial for molecular functions like protein interactions and trafficking.
- Viruses exploit these motifs to hijack host cells and facilitate their life cycle.
- Host enzymes targeting motifs are implicated in disease, yet motif mutations are not commonly observed in human disease.
Purpose of the Study:
- To investigate the apparent paradox of viral dependence on peptide motifs versus their apparent dispensability in host viability.
- To propose a model explaining why viruses exploit motifs while hosts tolerate their mutation.
Main Methods:
- Conceptual analysis of viral and host molecular strategies.
- Systems-level thinking applied to motif function and mutation impact.
Main Results:
- Viruses utilize short motifs as a principal mechanism for commandeering host machinery due to their small genome size.
- Host viability is not critically dependent on single motifs, suggesting a system-level architecture for motif utilization.
- This architecture allows viruses to exploit motifs without compromising essential host functions.
Conclusions:
- The proposed system-level architecture explains the differential impact of motif mutations on viral life cycles versus host viability.
- Understanding this system provides insights into viral pathogenesis and host-pathogen interactions.
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