In silico Determination of Host-Viral Interaction of Apoptotic Mimicry Pathway Proteins During Hepatitis B Viral Pathogenesis

Prachie Sharma(1), Kamal Rawal(2), kapila Kumar(3*)

(1) Manav Rachna International Institute of Research and Studies, Faridabad, 121003
(2) Amity Institute of Biotechnology, Amity University, Noida, 201308
(3) Manav Rachna International Institute of Research and Studies, Faridabad, 121003
(*) Corresponding Author


Viruses are the opportunistic pathogens that have developed several elegant strategies to deploy their host systems for a pathogenic invasion. Viral apoptotic mimicry is characterized by the exposure of host cell phospholipid, the phosphatidylserine which marks the host cell for apoptotic activation. The Hepatitis b virus, an enveloped virus has recently been found to interact with Phosphatidylserine (Ptdser) on the host through its large surface protein experimentally. Nonetheless, the employment of apoptotic mimicry during the pathogenesis of HBV has not been determined.  Therefore, in the present study, we attempt the in-silico exploration of the interaction of the apoptosis initiating receptors activated by Phosphatidylserine Receptors such as TIM3, AXL, MERTK and GAS6 by Hepatitis B Virus L protein. Molecular Docking of Phosphatidylserine Receptor were studied to observe protein – protein interaction against Surface L Protein of Hepatitis B Virus by using online protein  interaction software. It was found from the in-silico studies that Phosphatidylserine Receptors i.e. TIM3 (PDB: 5F71), AXL (PDB: 5U6B), MERTK (PDB: 2POC) and Gas6 (Growth Arrest Specific protein 6) (PDB: 2C5D) have shown effective binding efficacy against Surface L Protein of Hepatitis B Virus, whereas TIM3 (PDB: F71) and Gas6 (PDB: 2C5D) has shown maximum binding energy with respect to both the software used to analyse the protein-protein docking. This interaction study can form the basis of the experimental attempt in understanding the viral-host protein interaction pattern during hepatitis b viral infection.


Host viral PPI, Apoptotic Mimicry, Hepatitis B Virus, Phosphatidylserine Receptor, HEX 8.0 and ClusPro

Full Text:



Amara, A. & Mercer, J., 2015. Viral apoptotic mimicry. Nature Reviews Microbiology, 13(8), pp.461–469. doi: 10.1038/nrmicro3469.

Arandjelovic, S. & Ravichandran, K.S., 2015. Phagocytosis of apoptotic cells in homeostasis. Nature immunology, 16(9), pp.907–917. doi: 10.1038/ni.3253

Comeau, S.R. et al., 2004. ClusPro: a fully automated algorithm for protein-protein docking. Nucleic acids research 32(Web Server issue), pp.W96–W99. doi: 10.1093/nar/gkh354

Elliott, M.R. & Ravichandran, K.S., 2010. Clearance of apoptotic cells: implications in health and disease. The Journal of cell biology, 189(7), pp.1059–1070. doi: 10.1083/jcb.201004096.

Elmore, S., 2007. Apoptosis: a review of programmed cell death. Toxicologic pathology 35(4), pp.495–516. doi: 10.1080/01926230701320337.

Fadok, V.A. et al., 2001. Loss of Phospholipid Asymmetry and Surface Exposure of Phosphatidylserine Is Required for Phagocytosis of Apoptotic Cells by Macrophages and Fibroblasts. Journal of Biological Chemistry, 276(2), pp.1071–1077. doi: 10.1074/jbc.M003649200.

Gill, S.C. & von Hippel, P.H., 1989. Calculation of protein extinction coefficients from amino acid sequence data. Analytical Biochemistry, 182(2), pp.319–326. doi: 10.1016/0003-2697(89)90602-7

Guruprasad, K., Reddy, B.V.B. & Pandit, M.W., 1990. Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. Protein Engineering, Design and Selection, 4(2), pp.155–161. doi: 10.1093/protein/4.2.155.

IKAI, A., 1980. Thermostability and Aliphatic Index of Globular Proteins. The Journal of Biochemistry, 88(6), pp.1895–1898.

Kyte, J. & Doolittle, R.F., 1982. A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology, 157(1), pp.105–132. doi: 10.1016/0022-2836(82)90515-0

Laskowski, R.A. et al., 1993. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 26(2), pp.283–291. doi: 10.1107/S0021889892009944.

Lee, A.R. et al., 2022. Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System. Viruses, 14(2). doi: 10.3390/v14020373.

Lemke, G., 2017. Phosphatidylserine Is the Signal for TAM Receptors and Their Ligands. Trends in biochemical sciences, 42(9), pp.738–748. doi: 10.1016/j.tibs.2017.06.004.

Longdon, B. et al., 2014. The evolution and genetics of virus host shifts. PLoS pathogens, 10(11), e1004395. doi: 10.1371/journal.ppat.1004395.

Macindoe, G. et al., 2010. HexServer: an FFT-based protein docking server powered by graphics processors. Nucleic Acids Research, 38(Web Server issue), pp.W445-W449. doi: 10.1093/nar/gkq311

Maginnis, M.S., 2018. Virus-Receptor Interactions: The Key to Cellular Invasion. Journal of molecular biology, 430(17), pp.2590–2611. doi: 10.1016/j.jmb.2018.06.024.

Meertens, L. et al., 2012. The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry. Cell host & microbe, 12(4), pp. 544–557. doi: 10.1016/j.chom.2012.08.009.

Miaczynska, M. & Stenmark, H. 2008. Mechanisms and functions of endocytosis. The Journal of cell biology, 180(1), pp.7–11. doi: 10.1083/jcb.200711073.

Moller-Tank, S. & Maury, W., 2014. Phosphatidylserine receptors: enhancers of enveloped virus entry and infection. Virology, 468–470, pp.565–580. doi: 10.1016/j.virol.2014.09.009.

Vanlandschoot, P. & Leroux-Roels, G., 2003. Viral apoptotic mimicry: An immune evasion strategy developed by the hepatitis B virus? Trends in immunology, 24, pp.144–147. doi: 10.1016/S1471-4906(03)00026-7.

Wiederstein, M. & Sippl, M.J., 2007. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research, 35(suppl_2), pp.W407–W410. doi: 10.1093/nar/gkm290.

Yang, J. & Zhang, Y., 2015. I-TASSER server: new development for protein structure and function predictions. Nucleic acids research, 43(W1), pp.W174–W181. doi: 10.1093/nar/gkv342.


Article Metrics

Abstract views : 739 | views : 357


  • There are currently no refbacks.

Copyright (c) 2023 Journal of Tropical Biodiversity and Biotechnology

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Editoral address:

Faculty of Biology, UGM

Jl. Teknika Selatan, Sekip Utara, Yogyakarta, 55281, Indonesia

ISSN: 2540-9581 (online)