HPV and molecular mimicry in systemic lupus erythematosus and an impact of compiling B-cell epitopes and MHC-class II binding profiles with in silico evidence

Abstract

Epidemiological link between HPV and SLE is evolving. The possibility of HPV infection-induced molecular mimicry and systemic lupus erythematosus (SLE) was elucidated through detailed in silico analyses. Conserved regions in the structural protein sequences of high-risk HPV types were inferred, and sequence homologies between viral and human peptides were identified to delineate proteins implicated in SLE. B-cell epitopes and MHC-class II binding were compiled using Immune Epitope Database and ProPred II analysis tool. Molecular modeling and molecular dynamics/simulation (MDS) were performed using AutoDock Vina and GROMACS, respectively. Sequence alignment revealed 32 conserved regions, and 27/32 viral peptides showed varying similarities to human peptides, rich in B-cell epitopes with superior accessibility, high hydrophilicity, antigenicity and disposition to bind many class-II HLA alleles. Molecular docking of 13 viral peptides homologous (100%) to human peptides implicated in SLE showed that VIR-PEP1 (QLFNKPYWL) and VIR-PEP2 (DTYRFVTS) exhibited higher binding affinities than corresponding human peptides to SLE predisposing HLA-DRB1 allele. MDS of these peptides showed that the viral peptides had superior folding, compactness, and a higher number of hydrogen bonds than human peptides throughout the simulation period. SASA analysis revealed that the VIR-PEP1&2 fluctuated less frequently than corresponding human peptides. MM-PBSA revealed that the VIR-PEP2 complex exhibited higher binding energy than the human peptide complex. This suggests that highly conserved structural peptides of high-risk HPV types homologous to human peptides could compete and bind avidly to the HLA allele associated with SLE and predispose HPV-infected individuals to SLE through molecular mimicry.

Communicated by Ramaswamy H. Sarma

Keywords:

• Systemic lupus erythematosus
• HPV
• human leukocyte antigen
• peptides
• docking
• b-cell epitome
• molecular simulation

Acknowledgments

The published work is a part of the Ph.D. thesis of John Dickson Calvin D under The Tamil Nadu Dr. M.G.R. Medical University, Chennai and Tamil Nadu, India. The authors would like to thank Christian Medical College and Vellore Institute of Technology (VIT), Vellore, for providing the necessary facilities and subjects.

Authors’ Contribution

JDC, RJS, RK, PA, and JGF conceived the project, CJD, SRJ, FGJ, UKS, AB and CGPD were involved in the results’ acquisition, analysis, and interpretation. JDC, RJS, JGF, UKS and AB drafted the manuscript. All authors edited and approved the submitted version of the article.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

Fluid Research Grant (22 Z 438), Christian Medical College, Vellore.