Abstract
Polyethyleneimine (PEI) is a chemical compound that used is as a carrier in gene therapy/delivery. Some studies have investigated the microbicidal potential and antiviral activity (prophylactic or therapeutic) of PEI and its derivatives. The aim of this study was to investigate the effect of branched polyethyleneimine (bPEI) on human immunodeficiency virus (HIV) replication. Infected cells were treated with bPEI for 36 hours, and the concentration of the viral protein P24 (as a virus replication marker) was determined in cell culture supernatants. This study indicated that bPEI increased HIV replication and decreased the viability of infected cells through cytotoxicity. The toxicity of bPEI its association with and cell death (apoptosis, autophagy and necrosis) have been reported in several studies. To investigate bPEI-induced cytotoxicity, we examined apoptosis and autophagy in cells treated with bPEI, and a significant increase in HIV viral load, the P24 antigen level, autophagy, and necrosis observed. Thus, treatment with bPEI leads to cytotoxicity and higher HIV virus yield.
Similar content being viewed by others
References
Huh S-H, Do H-J, Lim H-Y, Kim D-K, Choi S-J, Song H, Kim N-H, Park J-K, Chang W-K, Chung H-M (2007) Optimization of 25 kDa linear polyethylenimine for efficient gene delivery. Biologicals 35:165–171
Khalil H, Chen T, Riffon R, Wang R, Wang Z (2008) Synergy between polyethylenimine and different families of antibiotics against a resistant clinical isolate of Pseudomonas aeruginosa. Antimicrob Agents Chemother 52:1635–1641
Spoden GA, Besold K, Krauter S, Plachter B, Hanik N, Kilbinger AF, Lambert C, Florin L (2012) Polyethylenimine is a strong inhibitor of human papillomavirus and cytomegalovirus infection. Antimicrob Agents Chemother 56:75–82
Moghimi SM, Symonds P, Murray JC, Hunter AC, Debska G, Szewczyk A (2005) A two-stage poly (ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapy. Mol Ther 11:990–995
Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24:1121–1131
Gao X, Yao L, Song Q, Zhu L, Xia Z, Xia H, Jiang X, Chen J, Chen H (2011) The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines. Biomaterials 32:8613–8625
Khan SZ, Hand N, Zeichner SL (2015) Apoptosis-induced activation of HIV-1 in latently infected cell lines. Retrovirology 12:42
Deretic V, Levine B (2009) Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5:527–549
Abdoli A, Alirezaei M, Mehrbod P, Forouzanfar F (2018) Autophagy: the multi‐purpose bridge in viral infections and host cells. Rev Med Virol 28(4):e1973
Aghasadeghi M, Zabihollahi R, Sadat S, Esfahani A, Ashtiani S, Namazi R, Kashanizadeh N, Azadmanesh K (2013) Production and evaluation of immunologic characteristics of mzNL4-3, a non-infectious HIV-1 clone with a large deletion in the pol-sequence. Mol Biol 47:228–235
Srivastava KK, Fernandez-Larsson R, Zinkus DM, Robinson HL (1991) Human immunodeficiency virus type 1 NL4-3 replication in four T-cell lines: rate and efficiency of entry, a major determinant of permissiveness. J Virol 65:3900–3902
Kafil V, Omidi Y (2011) Cytotoxic impacts of linear and branched polyethylenimine nanostructures in A431 cells. BioImpacts BI 1:23
Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A (2009) Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186:255–268
Zhang L, Zhang Y, Chen Z, He Y (2016) Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice. Int J Nanomed 11:5245
Matsuyama T, Hamamoto Y, Soma G-l, Mizuno D, Yamamoto N, Kobayashi N (1989) Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV): enhancement of HIV replication. J Virol 63:2504–2509
Sun L, Wang X (2014) A new kind of cell suicide: mechanisms and functions of programmed necrosis. Trends Biochem Sci 39:587–593
Wang X, Gao Y, Tan J, Devadas K, Ragupathy V, Takeda K, Zhao J, Hewlett I (2012) HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4+ T cells. Cell Signal 24:1414–1419
Lin C-W, Jan M-S, Kuo J-HS, Hsu L-J, Lin Y-S (2012) Protective role of autophagy in branched polyethylenimine (25K)-and poly (L-lysine)(30–70K)-induced cell death. Eur J Pharm Sci 47:865–874
Acknowledgements
We thank our colleagues in the Hepatitis and AIDS Department, Pasteur Institute of Iran, for their kind assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Handling Editor: Li Wu.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kandi, M.R., Mohammadnejad, J., Abdoli, A. et al. In vitro effect of branched polyethyleneimine (bPEI) on cells infected with human immunodeficiency virus: enhancement of viral replication. Arch Virol 164, 3019–3026 (2019). https://doi.org/10.1007/s00705-019-04426-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00705-019-04426-3