Contrasting interferon-mediated antiviral responses in human lung adenocarcinoma cells Article Swipe
Matthew A. Esparza
,
Sara S. El Zahed
,
Umut Karakus
,
Hanspeter Niederstrasser
,
Boning Gao
,
Kimberly Batten
,
Jerry W. Shay
,
Bruce A. Posner
,
Fred R. Hirsch
,
Luc Girard
,
Lily Huang
,
John D. Minna
,
Adolfo Garcı́a-Sastre
,
Beatriz M. A. Fontoura
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1128/jvi.00469-25
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1128/jvi.00469-25
Lung cancers develop from lung epithelial cells after a series of genetic and epigenetic changes, and these cells are major sites of influenza virus infection. Thus, we explored how changes found in patient-derived lung cancer cell lines impacted influenza virus replication and identified two lines with opposite responses to influenza A viral infection. We show that the NCI-H820 lung adenocarcinoma (LUAD) is resistant to influenza A virus and VSV infection, while LUAD line NCI-H322 is highly susceptible to infection by both viruses. H322 cells have a homozygous deletion in a region of chromosome 9 encoding IFNαgenes, IFNβ1, IFNω1, and IFNε genes, leading to downregulation of immune response and high infection rates. In contrast, the resistant H820 cell line has three copies of these same interferon genes and shows increased expression of interferon-regulated genes. We found that the resistance of H820 cells to influenza infection is likely linked to impaired viral entry—due to high basal levels of interferon-induced proteins known to inhibit endocytosis (IFITM1/2/3, NCOA7, and CH25H)—and to increased expression of mRNAs that encode other antiviral factors. In contrast, H322 cells show the absence or low levels of interferon-regulated genes involved in the inhibition of viral entry. These results suggest that the opposite phenotypes on viral entry of H322 and H820 cells may be at least in part associated with impaired or enhanced interferon response, respectively. Since most lung cancer patients have genomic characterization of their tumors, individualized differences in interferon responses may have therapeutic and patient management implications. IMPORTANCE Lung cancers develop from genetic and epigenetic changes that can dramatically influence patients’ susceptibility to viral infection and replication. This study evaluates the responses to influenza virus infection of two patient-derived lung cancer cell lines. Interestingly, the cell lines investigated are of the same cancer type, lung adenocarcinomas, yet one cell line is highly susceptible, while the other cell line is highly resistant to viral infection. This is in part due to contrasting genetic alterations that lead to changes in the interferon response pathways, which differentially impact viral entry. Thus, identifying these risk factors can inform the prognosis of patients infected with influenza virus and guide their personalized treatment plans.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/jvi.00469-25
- OA Status
- diamond
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410823794
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410823794Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1128/jvi.00469-25Digital Object Identifier
- Title
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Contrasting interferon-mediated antiviral responses in human lung adenocarcinoma cellsWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-05-28Full publication date if available
- Authors
-
Matthew A. Esparza, Sara S. El Zahed, Umut Karakus, Hanspeter Niederstrasser, Boning Gao, Kimberly Batten, Jerry W. Shay, Bruce A. Posner, Fred R. Hirsch, Luc Girard, Lily Huang, John D. Minna, Adolfo Garcı́a-Sastre, Beatriz M. A. FontouraList of authors in order
- Landing page
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https://doi.org/10.1128/jvi.00469-25Publisher landing page
- Open access
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YesWhether a free full text is available
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diamondOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1128/jvi.00469-25Direct OA link when available
- Concepts
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Biology, Interferon, Virus, Virology, Influenza A virus, Cell culture, Viral replication, Immune system, Immunology, Cancer research, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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45Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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