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#Influenza A Virus #infection is associated with TDP-43 #pathology and neuronal #damage in the #brain

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By G.M.

Abstract

Viral pandemics such as COVID-19 have demonstrated long-term neurological consequences, including memory impairment and depression, emphasizing the importance of understanding virus-brain interactions [1]. Similar concerns have been raised for Influenza A virus (IAV), which has been implicated in neurodegenerative disorders [2, 3]. In this study, we investigated the neuropathological effects of highly pathogenic avian influenza (HPAI) H5N1 and H5N8 strains in a mouse model. Although viral RNA was detected in the brain post-infection, no viral proteins were found, suggesting limited or transient brain replication. Despite this, infected brains showed significant neuronal damage, including axonal loss and nuclear condensation, as evidenced by immunofluorescence and Nissl staining. We also observed pathological changes in TDP-43, including conformational alterations and increased phosphorylation, which required antigen retrieval for detection, features reminiscent of those found in frontotemporal dementia and amyotrophic lateral sclerosis [4, 5]. Transcriptomic analysis further revealed strain-specific host responses, including activation of interferon-related genes and downregulation of microtubule-associated pathways. These findings suggest that IAV infection can trigger hallmarks of neurodegeneration in the absence of persistent viral protein expression, possibly through host-driven mechanisms. Our results underscore the need for further investigation into virus-induced molecular pathways contributing to neurodegenerative disease.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.30.662477v1

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