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Higher replication potential of West Nile virus governs apoptosis induction in human neuroblastoma cells

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Abstract

The extent of neuronal cell damage caused by West Nile virus (WNV) infection governs the disease severity ranging from mild, febrile illness to fatal encephalitis. Availability of naturally occurring genetic variants is helpful to study viral factors governing differential pathogenesis. During WNV infection, apoptosis serves as a virulence determinant positively contributing to viral pathogenesis. We investigated the levels of apoptosis induced by a low neurovirulent WNV lineage 5 strain 804994 and a high neurovirulent lineage 1 strain 68856 in human neuroblastoma cells, IMR-32. Our investigations clearly show the correlation between higher multiplication capacities of 68856 with higher levels of cytopathology induced by apoptosis. We observed activation of both the extrinsic and intrinsic apoptotic pathways during WNV infection. Infection with higher neurovirulent strain resulted in higher upregulation of pro-apoptotic proteins including death receptors (DR), adaptor protein, BH3-only regulatory proteins and higher cleavage of initiator caspases of both pathways. These results suggest that the virulence of a WNV strain may correlate with its higher replication fitness and ability to cause more cellular damage.

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The data generated during and analysed during this study is included in the supplementary file, which will be available from the corresponding author on reasonable request.

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Acknowledgements

Authors are thankful to the Director, ICMR-NIV, Pune for continuous support and critical evaluation of the work. We are grateful to the technical and scientific staff of the Encephalitis Group for providing active support and critique during the work. We are also thankful to the Director General, ICMR and CSIR, New Delhi, India and for financial support (project ID: ENC1304).

Funding

Research work was funded by Indian Council of Medical Research (ICMR, NIV ID: ENC1304).

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  1. Encephalitis Group, ICMR-National Institute of Virology, Pashan – Sus Road, Pune, Maharashtra, 411021, India

    Sonal Mundhra & Vijay P. Bondre

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  1. Sonal Mundhra
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SM performed all the experiments, data analysis and manuscript writing; VPB conceived concept, planning and supervising of experiments, data analysis and manuscript editing.

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Correspondence to Vijay P. Bondre.

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Study was approved by the Institutional Biosafety Committee, ICMR-NIV, Pune (IBSC:2013–39). This study does not involve any animal experiments while the standard antiviral sera was procured from Virus Registry, ICMR-NIV, Pune.

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Mundhra, S., Bondre, V.P. Higher replication potential of West Nile virus governs apoptosis induction in human neuroblastoma cells. Apoptosis 28, 1113–1127 (2023). https://doi.org/10.1007/s10495-023-01844-2

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