Predictive and comparative analysis of Ebolavirus proteins
Qian Cong1, Jimin Pei, Nick V Grishin
1a Departments of Biophysics and Biochemistry ; University of Texas Southwestern Medical Center at Dallas ; Dallas , TX USA.
Cell Cycle (Georgetown, Tex.)
|July 10, 2015
Summary
Computational analysis of Ebolavirus proteins reveals potential determinants of pathogenicity and host specificity. Understanding these viral and host protein interactions is crucial for combating Ebola Hemorrhagic Fever (EHF).
Area of Science:
- Virology and Structural Biology
- Computational Biology and Bioinformatics
Background:
- Ebolavirus causes Ebola Hemorrhagic Fever (EHF), a high-fatality disease with recent epidemic outbreaks.
- Reston ebolavirus (RESTV) is non-pathogenic in humans but causes EHF in macaques, offering insights into pathogenicity.
- Understanding Ebolavirus protein structures and host interactions is vital for therapeutic development.
Purpose of the Study:
- To predict 3D structures and functional sites of Ebolavirus protein domains with unknown structures using computational analysis.
- To identify host protein sequence variations linked to RESTV resistance and susceptibility in primates.
- To investigate sequence variations associated with RESTV's loss of human pathogenicity and map them onto 3D structures.
Main Methods:
- Applied computational analysis to predict 3D structures of Ebolavirus protein domains (VP30, protein L).
- Compared protein sequences interacting with Ebolavirus proteins between RESTV-resistant and RESTV-susceptible primates.
- Mapped identified sequence variations onto predicted 3D structures and compared them with known functional sites.
Main Results:
- Predicted 3D structures and functional sites for previously uncharacterized Ebolavirus protein domains.
- Identified significant sequence divergence in host proteins interacting with GP and VP35 between resistant and susceptible primates, suggesting a role in host specificity.
- Detected variable positions in viral proteins, particularly VP35 and VP30, associated with lost human pathogenicity in RESTV, with surface clustering indicating potential uncharacterized host interaction sites.
Conclusions:
- Computational predictions provide insights into Ebolavirus protein structures and functional sites.
- Host protein divergence in interactions with GP and VP35 may explain species-specific pathogenicity.
- Identified viral protein variations and their structural mapping offer targets for understanding and potentially mitigating Ebolavirus virulence.
