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bioRxiv · 10.1101/2022.10.10.511685

Newcastle disease virus elevates its replication by instigating oxidative stress-driven Sirtuin 7 production

Shokeen, K.·Kumar, S.
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Abstract

Reactive oxygen species (ROS) accumulation inside the cells instigates oxidative stress leading to the activation of stress-responsive genes. The persistence of stress halts the cells antiviral response, from which numerous viruses benefit. The viral strategies for promoting stressful conditions and utilizing the induced host proteins to enhance their replication remain elusive. The present work investigates the impact of oxidative stress on NDV pathogenesis. Here, we report that the progression of NDV infection depends on intracellular ROS production. Additionally, the results demonstrate the elevation of SIRT7 levels at transcription and translational levels post-NDV infection, which in turn is associated with the positive regulation of cellular protein deacetylation. A detailed mechanistic study in vitro and in ovo was also carried out utilizing SIRT7 activity modulators to decipher the underlying role in infection, either constructive or destructive. Lastly, we concluded that the elevated expression of NDV-mediated SIRT7 protein with an enhanced activity metabolizes the NAD+ to deacetylase the host proteins, thus contributing to high virus replication. ImportanceAlthough the instigation of oxidative stress during NDV infection has been reported several times, the cellular stress-responsive proteins direct function in virus replication is yet to be well understood. This study highlights the plausible stress-responsive proteins involved in viral pathogenesis while exploring the detailed molecular mechanisms of crosstalk between the activated cellular protein and the progress of the NDV replication cycle. Moreover, previous studies describing how different viruses modulate cellular stress may not fully reflect the complete picture of viral strategies. Here, we demonstrate NDV-influenced active involvement of SIRT7 activity leading to the deacetylation of host proteins. It helped us better understand the viruss strategies to generate its numerous copies while perturbing the host cells standard functionality and opening up new possibilities for infection interventions.

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Shokeen, K., Kumar, S.. 2022-10-11. Newcastle disease virus elevates its replication by instigating oxidative stress-driven Sirtuin 7 production. https://doi.org/10.1101/2022.10.10.511685

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