Work

Dissecting Cell Death Pathways in Influenza A Virus Infection: Comparative Insights from Human Models

Year: 2026

Type: article

Abstract: Influenza A virus remains a major global health threat, causing annual epidemics and occasional pandemics. Programmed cell death, including apoptosis, pyroptosis, and necroptosis, with emerging evidence for ferroptosis, plays a dual role in influenza pathogenesis, both limiting viral replication and contributing to immunopathology. Most mechanistic insights have been derived from murine genetic models, which have been invaluable for establishing causal roles of these pathways. However, murine models and cancer-derived cell lines differ significantly from human physiology. This review systematically compares influenza-induced programmed cell death across human-relevant platforms, including primary cells, immortalized non-cancerous lines, co-cultures, organoids, and precision-cut lung slices. The increasing complexity of these models reveals distinct aspects of pathway activation, bystander effects, cell-type vulnerability, and spatial dynamics. We highlight critical divergences between model systems, identify gaps in comparative analyses across viral strains and experimental platforms, and outline future directions leveraging advanced model systems, multi-omics, and functional genomics to enhance translational relevance and guide the development of host-directed therapies.

Source: Viruses

DOI: 10.3390/v18020246

Authors: Ngoc Mai Khoi Nguyen, Alison C. West, Rebecca L. Ambrose, Michelle D. Tate

Institutions: Hudson Institute of Medical Research, Monash University

Language: English

Topic: Influenza Virus Research Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,137