Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors.

TitleMeta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors.
Publication TypeJournal Article
Year of Publication2021
AuthorsChen, F, Zhang, Y, Sucgang, R, Ramani, S, Corry, D, Kheradmand, F, Creighton, CJ
JournalSci Rep
Volume11
Issue1
Pagination2459
Date Published2021 01 28
ISSN2045-2322
KeywordsA549 Cells, Bronchi, COVID-19, Epithelial Cells, Host Microbial Interactions, Humans, Immunity, Lung Neoplasms, SARS-CoV-2, Transcription, Genetic, Transcriptome, Virus Replication
Abstract

A deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.

DOI10.1038/s41598-021-82221-4
Alternate JournalSci Rep
PubMed ID33510359
PubMed Central IDPMC7844278
Grant ListR01AI135803 / NH / NIH HHS / United States
R01 ES029442 / ES / NIEHS NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
R01 AI135803 / AI / NIAID NIH HHS / United States
CA125123 / NH / NIH HHS / United States
R01ES029442-01 / NH / NIH HHS / United States
U19 AI144297 / AI / NIAID NIH HHS / United States
U19AI144297 / NH / NIH HHS / United States