GEO series

Host transcriptome in human lung A549 cells infected with SARS-CoV-2 expressing wild-type and mutant (H234A and N277A) Nsp15

GSE274310 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2025/12/31 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 24 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 24 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Coronavirus (CoV) Nsp15 is a viral endoribonuclease (EndoU) with a preference for uridine residues. CoV Nsp15 is an innate immune antagonist which prevents dsRNA sensor recognition and stress granule formation by targeting viral and host RNAs. SARS-CoV-2 restricts and delays the host antiviral innate immune responses through multiple viral proteins, but the role of SARS-CoV-2 Nsp15 in innate immune evasion is not completely understood.

Read the full summary ↓

Here, we generate an EndoU activity knockout rSARS-CoV-2Nsp15-H234A to elucidate the biological functions of Nsp15. Relative to wild-type rSARS-CoV-2, replication of rSARS-CoV-2Nsp15-H234A was significantly decreased in IFN-responsive A549-ACE2 cells but not in its STAT1 knockout counterpart. Transcriptomic analysis revealed upregulation of innate immune response genes in cells infected with rSARS-CoV-2Nsp15-H234A relative to wild-type virus, including cGAS-STING, cytosolic DNA sensors activated by both DNA and RNA viruses. Treatment with STING inhibitors H-151 and SN-011 rescued the attenuated phenotype of rSARS-CoV-2Nsp15-H234A. SARS-CoV-2 Nsp15 inhibited cGAS-STING-mediated IFN-β promoter and NF-κB reporter activity, as well as facilitated the replication of EV-D68 and NDV by diminishing the expression of cGAS and STING and downstream innate immune responses. Notably, the decline in cGAS and STING was also apparent during SARS-CoV-2 infection. The EndoU activity was essential for SARS-CoV-2 Nsp15-mediated cGAS and STING downregulation, but not all HCoV Nsp15 share the consistent substrate selectivity. In the hamster model, rSARS-CoV-2Nsp15-H234A replicated to lower titers in the nasal turbinates and lungs and induced higher innate immune responses. Collectively, our findings exhibit that SARS-CoV-2 Nsp15 serves as a host innate immune antagonist by targeting host cGAS and STING.

This dataset

Open GSE274310 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE274310_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1143096 and SRA study SRP523755. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

8 conditions, mostly in triplicate

A549-ACE2, mock, 8hpi, ×3 A549-ACE2, WT, 8hpi, ×3 A549-ACE2, H234A, 8hpi, ×3 A549-ACE2, N277A, 8hpi, ×3 A549-ACE2, mock, 24hpi, ×3 A549-ACE2, WT, 24hpi, ×3 A549-ACE2, H234A, 24hpi, ×3 A549-ACE2, N277A, 24hpi, ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8447165 A549-ACE2, mock, 8hpi, rep1 A549-ACE2, mock, 8hpi,
GSM8447166 A549-ACE2, mock, 8hpi, rep2 A549-ACE2, mock, 8hpi,
GSM8447167 A549-ACE2, mock, 8hpi, rep3 A549-ACE2, mock, 8hpi,
GSM8447168 A549-ACE2, WT, 8hpi, rep1 A549-ACE2, WT, 8hpi,
GSM8447169 A549-ACE2, WT, 8hpi, rep2 A549-ACE2, WT, 8hpi,
GSM8447170 A549-ACE2, WT, 8hpi, rep3 A549-ACE2, WT, 8hpi,
GSM8447171 A549-ACE2, H234A, 8hpi, rep1 A549-ACE2, H234A, 8hpi,
GSM8447172 A549-ACE2, H234A, 8hpi, rep2 A549-ACE2, H234A, 8hpi,
GSM8447173 A549-ACE2, H234A, 8hpi, rep3 A549-ACE2, H234A, 8hpi,
GSM8447174 A549-ACE2, N277A, 8hpi, rep1 A549-ACE2, N277A, 8hpi,
GSM8447175 A549-ACE2, N277A, 8hpi, rep2 A549-ACE2, N277A, 8hpi,
GSM8447176 A549-ACE2, N277A, 8hpi, rep3 A549-ACE2, N277A, 8hpi,
GSM8447177 A549-ACE2, mock, 24hpi, rep1 A549-ACE2, mock, 24hpi,
GSM8447178 A549-ACE2, mock, 24hpi, rep2 A549-ACE2, mock, 24hpi,
GSM8447179 A549-ACE2, mock, 24hpi, rep3 A549-ACE2, mock, 24hpi,
GSM8447180 A549-ACE2, WT, 24hpi, rep1 A549-ACE2, WT, 24hpi,
GSM8447181 A549-ACE2, WT, 24hpi, rep2 A549-ACE2, WT, 24hpi,
GSM8447182 A549-ACE2, WT, 24hpi, rep3 A549-ACE2, WT, 24hpi,
GSM8447183 A549-ACE2, H234A, 24hpi, rep1 A549-ACE2, H234A, 24hpi,
GSM8447184 A549-ACE2, H234A, 24hpi, rep2 A549-ACE2, H234A, 24hpi,
GSM8447185 A549-ACE2, H234A, 24hpi, rep3 A549-ACE2, H234A, 24hpi,
GSM8447186 A549-ACE2, N277A, 24hpi, rep1 A549-ACE2, N277A, 24hpi,
GSM8447187 A549-ACE2, N277A, 24hpi, rep2 A549-ACE2, N277A, 24hpi,
GSM8447188 A549-ACE2, N277A, 24hpi, rep3 A549-ACE2, N277A, 24hpi,

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