Contrasting interferon-mediated antiviral responses in human lung adenocarcinoma cells

Matthew Esparza ¹, Sara S El Zahed ^2,3, Umut Karakus ^2,3

¹Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
²Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁵Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁶Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁷Center for Thoracic Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁹Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
¹¹Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹²The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

⁰Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Journal of Virology +

|

May 28, 2025

View abstract on PubMed

Summary

Lung cancer cell lines show differing responses to influenza A virus infection due to genetic changes affecting interferon pathways. Understanding these differences can guide personalized treatment for lung cancer patients with viral infections.

Area Of Science

Virology
Oncology
Immunology

Background

Lung cancers arise from genetic and epigenetic alterations in lung epithelial cells.
These cellular changes can impact susceptibility to viral infections, including influenza.
Patient-derived lung cancer cell lines offer models to study virus-host interactions.

Purpose Of The Study

To investigate how genetic alterations in lung adenocarcinoma cell lines affect influenza A virus replication.
To compare the differential responses of two lung cancer cell lines to influenza virus infection.
To elucidate the role of interferon pathways in mediating differential viral susceptibility.

Main Methods

Utilized two patient-derived lung adenocarcinoma (LUAD) cell lines: NCI-H820 (resistant) and NCI-H322 (susceptible).
Analyzed genetic makeup, focusing on interferon (IFN) gene copy number and expression.
Assessed viral replication and expression of interferon-regulated genes involved in viral entry inhibition.

Main Results

NCI-H820 cells exhibit resistance to influenza A virus and VSV, possessing multiple copies of IFN genes and high expression of antiviral factors (IFITM1/2/3, NCOA7, CH25H).
NCI-H322 cells are highly susceptible, with a homozygous deletion of key IFN genes, leading to impaired interferon response and viral entry.
Differential expression of interferon-regulated genes correlates with contrasting viral entry phenotypes in the two cell lines.

Conclusions

Genetic variations in interferon gene copy number and expression significantly influence influenza virus susceptibility in lung cancer cells.
Interferon response pathways, particularly those affecting viral entry, play a critical role in determining differential viral infection outcomes.
Genomic characterization of lung tumors may reveal patient-specific interferon response profiles, informing prognosis and personalized therapeutic strategies.

Keywords:

influenza interferons lung cancer viral entry

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