The Role of Dengue Virus Nonstructural Protein 1 (NS1) on Cell Apoptosis through Caspase-3 Activation and Mitochondrial Dysfunction

Riyanda Indrawan Sani, Fakultas Kedokteran dan Ilmu Kesehatan Universitas Muhammadiyah Sumatera Utara, Nurfadly Nurfadly, Fakultas Kedokteran dan Ilmu Kesehatan Universitas Muhammadiyah Sumatera Utara, Zukhrofi Muzar, Fakultas Kedokteran dan Ilmu Kesehatan Universitas Muhammadiyah Sumatera Utara, Shahrul Rahman, Fakultas Kedokteran dan Ilmu Kesehatan Universitas Muhammadiyah Sumatera Utara, Siti Masliana Siregar, Fakultas Kedokteran dan Ilmu Kesehatan Universitas Muhammadiyah Sumatera Utara
Received: 2026-03-10
Accepted: 2026-08-05
Published: 2026-11-02

Abstract


Dengue Virus (DENV) infection can lead to neurological complications, with the NS1 protein implicated in pathogenesis, though its mechanisms remain unclear. This study investigated the effect of NS1 on Caspase-3 mRNA expression and mitochondrial function in peripheral blood mononuclear cells (PBMCs). PBMCs isolated from healthy donors were exposed to NS1 protein. Caspase-3 mRNA levels were measured using RT-PCR, and mitochondrial function was assessed via JC-1 staining. Results demonstrated that NS1 exposure significantly increased Caspase-3 mRNA expression (control Ct 31.37±0.24 vs. 24.58±0.70) and induced marked mitochondrial dysfunction at concentrations of 1 ng/mL (mean=0.21; p=0.022) and 5 ng/mL (mean=0.20; p=0.028). These findings indicate that DENV NS1 activates apoptotic pathways by upregulating Caspase-3 and disrupting mitochondrial function. This study provides new insights into DENV-induced cellular damage and suggests potential for developing Caspase-3-targeted therapies for dengue-associated neurological complications.

Keywords


Apoptosis; Caspase-3; Dengue virus; Mitochondrial dysfunction; NS1 protein

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References


Mustafa MS, Rasotgi V, Jain S, Gupta V. Discovery of fifth serotype of dengue virus (DENV-5): A new public health dilemma in dengue control. Med J Armed Forces India 2015;71(1):67–70.

Barcellos C, Matos V, Lana RM, Lowe R. Climate change, thermal anomalies, and the recent progression of dengue in Brazil. Sci Rep 2024;14(1):5948.

Holbrook MR. Historical Perspectives on Flavivirus Research. Viruses 2017;9(5).

Colón-González FJ, Gibb R, Khan K, Watts A, Lowe R, Brady OJ. Projecting the future incidence and burden of dengue in Southeast Asia. Nat Commun 2023;14(1):5439.

Wilder-Smith A, Ooi E-E, Horstick O, Wills B. Dengue. The Lancet 2019;393(10169):350–363.

Tantawichien T. Dengue fever and dengue haemorrhagic fever in adolescents and adults. Paediatr Int Child Health 2012;32(sup1):22–27.

Datta S, Wattal C. Dengue NS1 antigen detection: A useful tool in early diagnosis of dengue virus infection. Indian J Med Microbiol 2010;28(2):107–110.

Malavige GN, Ogg GS. Pathogenesis of vascular leak in dengue virus infection. Immunology 2017;151(3):261–269.

Prabhat N, Ray S, Chakravarty K, et al. Atypical neurological manifestations of dengue fever: a case series and mini review. Postgrad Med J 2020;96(1142):759–765.

Calderón-Peláez M-A, Velandia-Romero ML, Bastidas-Legarda LY, Beltrán EO, Camacho-Ortega SJ, Castellanos JE. Dengue Virus Infection of Blood–Brain Barrier Cells: Consequences of Severe Disease. Front Microbiol 2019;10.

Trivedi S, Chakravarty A. Neurological Complications of Dengue Fever. Curr Neurol Neurosci Rep 2022;22(8):515–529.

Singh PK, Sheoran A, Tetarwal P, Singh P, Singh P. Dengue Hemorrhagic Encephalitis in Dengue Epidemic. J Glob Infect Dis 2023;15(1):37–38.

Varatharaj A. Encephalitis in the clinical spectrum of dengue infection. Neurol India 2010;58(4):585.

Kalane SU, Gokhale AN, Kalane UD. Dengue Encephalitis in a Newborn. Indian J Pediatr 2021;88(7):716–716.

Maheshwari A, Singh S, Amrit A, Alallah J, Boppana S. Neurological Manifestations of Perinatal Dengue. Newborn 2023;2(2):158–172.

Chen H-R, Lai Y-C, Yeh T-M. Dengue virus non-structural protein 1: a pathogenic factor, therapeutic target, and vaccine candidate. J Biomed Sci 2018;25(1):58.

Fisher R, Lustig Y, Sklan EH, Schwartz E. The Role of NS1 Protein in the Diagnosis of Flavivirus Infections. Viruses 2023;15(2).

Muller DA, Young PR. The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker. Antiviral Res 2013;98(2):192–208.

Pan Y, Cheng A, Wang M, Yin Z, Jia R. The Dual Regulation of Apoptosis by Flavivirus. Front Microbiol 2021;12.

Tripathi S, Sengar S, Shree B, Mohapatra S, Basu A, Sharma V. An RBM10 and NF-κB interacting host lncRNA promotes JEV replication and neuronal cell death. J Virol 2023;97(12):e0118323.

Castellanos JE, Neissa JI, Camacho SJ. La infección con el virus del dengue induce apoptosis en células del neuroblastoma humano SH-SY5Y. Biomédica 2016;36:156.




DOI: https://doi.org/10.30596/jih.v7i4.29537

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