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Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
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Positive Selection Drives Evolution at the Host-Filovirus Interaction Surface.
Chiara Pontremoli1, Diego Forni1, Rachele Cagliani1
1Scientific Institute IRCCS E.MEDEA, Bioinformatics, Bosisio Parini, Italy.
Molecular Biology and Evolution
|August 12, 2016
Summary
Filovirus infection relies on the interaction between the virus glycoprotein (GP) and the host cell receptor Niemann-Pick C1 (NPC1). Both GP and NPC1-C evolve under selective pressures, indicating an ongoing evolutionary arms race.
Area of Science:
- Evolutionary Biology
- Virology
- Molecular Biology
Background:
- Filovirus infection depends on the interaction between the viral glycoprotein (GP) and the host cell receptor Niemann-Pick C1 (NPC1).
- Specifically, two loops in the C domain of NPC1 (NPC1-C) are crucial for binding filovirus GP.
Purpose of the Study:
- To investigate the co-evolutionary dynamics between filovirus GP and its host receptor NPC1.
- To identify sites under selective pressure in both filovirus GP and NPC1 across mammalian evolution.
Main Methods:
- Phylogenetic analysis of mammalian NPC1 sequences.
- Identification of positively and negatively selected sites in NPC1 and filovirus GP.
- Analysis of co-evolving sites and their functional implications.
Main Results:
- NPC1-C and filovirus GP evolve under mutual selective pressure, despite functional constraints on NPC1.
- Positive selection was detected in NPC1-C across all mammalian orders, with specific adaptive changes in different lineages, including a potential human-specific adaptation (T419I).
- Filovirus GP also shows adaptive evolution, with selected sites impacting NPC1 binding and antibody epitopes, suggesting immune response as a key driver.
Conclusions:
- The host-pathogen interaction between filoviruses and NPC1 is shaped by a continuous evolutionary arms race.
- Host humoral immunity plays a significant role in filovirus evolution and speciation.
- Specific variants like S142Q in GP may influence Ebolavirus host range and reservoir dynamics.
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