Computational analysis of Non-synonymous SNP effects on human PLVAP gene structure and function

Area of Science:

• Genomics and Bioinformatics
• Virology
• Molecular Biology

Background:

• Plasmalemma vesicle-associated protein (PLVAP) is crucial for blood-brain barrier (BBB) integrity and serves as a receptor for Japanese Encephalitis Virus (JEV).
• Understanding how genetic variations in PLVAP affect JEV neuroinvasion is vital for disease prevention and treatment.

Purpose of the Study:

• To computationally analyze the functional impact of non-synonymous single-nucleotide polymorphisms (nsSNPs) in the PLVAP gene on JEV-host interactions.
• To identify specific PLVAP variants that influence JEV binding and entry into the central nervous system.

Main Methods:

• Retrieved and analyzed 11,883 SNPs from NCBI dbSNP, identifying 403 unique nsSNPs.
• Performed protein stability, disorder, conservation, and molecular docking analyses to assess variant impact.
• Prioritized five critical nsSNPs (R26H, I35T, E175G, V44G, I39S) based on their predicted effects.

Main Results:

• Identified 43 nsSNPs significantly destabilizing PLVAP structure and 29 deleterious nsSNPs.
• Five critical variants demonstrated pronounced destabilizing effects and altered PLVAP-JEV binding interactions.
• Mutations were predicted to modify JEV entry efficiency and host susceptibility.

Conclusions:

• PLVAP variants can influence JEV neuroinvasion, suggesting their potential as biomarkers for risk stratification.
• Findings support therapeutic strategies targeting PLVAP-JEV interactions for antiviral drug discovery.
• The computational approach can be extended to other flavivirus-host interactions for personalized medicine.