Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 12, 2026 56 minutes ago
Scientists have uncovered an unexpected way SARS-CoV-2 may activate one of the body’s important antiviral defenses. Rather than simply recognizing genetic material belonging to the virus, the immune sensor MDA5 appears able to detect disruptions that infection causes to the cell’s own RNA-processing system.
SARS-CoV-2 disrupts normal cellular RNA processing, producing abnormal host RNA that may trigger activation of
the antiviral sensor MDA5.
The discovery suggests that infected cells may effectively reveal the presence of SARS-CoV-2 through the molecular disorder the virus creates inside them.
Researchers From Multiple International Institutions
The researchers were from the Medical Research Council Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine and Radcliffe Department of Medicine at the University of Oxford, United Kingdom; Hudson Institute of Medical Research and Monash University, Australia; Institut de Recherche en Infectiologie de Montpellier, CNRS and University of Montpellier, France; IMol Polish Academy of Sciences, Poland; and Åbo Akademi University, Finland.
MDA5 Was Mainly Binding Human RNA
MDA5 is an immune sensor located primarily in the cytoplasm, the area of the cell outside its nucleus. It helps initiate production of type I interferons and other antiviral molecules when potentially dangerous RNA is detected.
Using a highly precise technique called iCLIP, researchers examined RNA physically associated with MDA5 in SARS-CoV-2-infected human Calu-3 lung epithelial cells.
The findings were surprising. Although approximately 10 percent of RNA sequences in infected-cell input samples mapped to SARS-CoV-2, researchers found no enrichment of SARS-CoV-2 RNA among the RNA captured with MDA5. Instead, MDA5 binding sites were detected in the cell’s own RNA.
More than 50 percent of these binding sites occurred within introns—sections of newly produced RNA normally removed during RNA splicing. Around 25 percent occurred in intergenic regions and roughly 10 percent in protein-coding regions.
SARS-CoV-2 Creates Abnormal Cellular RNA
Researchers found that SARS-CoV-2 infection increased abnormal transcripts and intron-containing RNA within the cytoplasm. Importantly, introns that accumulated during viral infection were more likely to overlap with regions bound by MDA5.
As explained in this Thailand
Medical News report, the findings suggest MDA5 may act partly as a cellular quality-control sensor. Instead of relying entirely on direct recognition of viral RNA, MDA5 can potentially detect the consequences of viral interference with normal cellular RNA processing.
Many MDA5-bound introns were unusually long, frequently represented the first intron of a gene and possessed weaker splicing signals or less favorable branch-point characteristics. These features make proper removal of introns more difficult, increasing the likelihood that improperly p
rocessed RNA will remain behind.
Researchers also found an association with repetitive RNA sequences. Around 30 percent of MDA5 binding sites during SARS-CoV-2 infection occurred within repetitive regions, while approximately half of the larger RNA regions surrounding binding sites overlapped with Alu repeats.
Restoring RNA Processing Reduced MDA5 Activation
Further experiments using encephalomyocarditis virus provided important functional evidence. Researchers increased levels of SRSF3, a protein involved in RNA splicing and messenger RNA export.
Increasing SRSF3 reduced abnormal RNA transcription and processing and weakened the MDA5-dependent type I interferon response. Crucially, viral replication itself was not reduced, supporting the idea that improved RNA processing—not simply lower amounts of virus—was responsible for the diminished immune activation.
Conclusions
The findings reshape the traditional view of MDA5 as primarily a detector of foreign viral RNA. MDA5 may also monitor cellular RNA homeostasis and recognize improperly processed host RNA generated when viruses disturb normal splicing and other post-transcriptional processes. This mechanism could help explain how MDA5 detects very different infections, including situations where viral RNA is protected inside specialized replication structures. Further research is needed to establish how broadly this mechanism operates across different viruses, tissues and stages of infection.
The study findings were published in the peer reviewed journal: Nature Immunology.
https://www.nature.com/articles/s41590-026-02614-3
Read Also:
https://www.thailandmedical.news/articles/coronavirus
https://www.thailandmedical.news/articles/long-covid
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