Recent research from The Francis Crick Institute, University of Glasgow Centre for Virus Research, and University College London has revealed how SARS-CoV-2 adapts to evade immune responses. The study focuses on the emergence of subgenomic RNAs, which enhance the virus's fitness.
Subgenomic RNAs are small sections of genetic material that allow viruses to produce proteins crucial for replication. This study identified transcription regulatory sequences (TRSs) that guide the synthesis of these RNAs.
New TRSs have emerged in SARS-CoV-2, particularly in variants like Alpha and Omicron, leading to novel subgenomic RNAs. These RNAs disrupt type I interferon production, a key component of the body's antiviral defense.
Key findings include:
Emergence of New TRSs: Discovered in over 60% of global SARS-CoV-2 samples, particularly in Alpha and Omicron variants.
Function of Novel RNA: Generates a protein called N.iORF3, which weakens the immune response.
Prevalence in Human Infections: Confirmed in clinical samples from patients infected with Alpha and Omicron variants.
Distinct Role in Viral Fitness: Viruses with these TRSs replicate more efficiently in human cells.
Convergent Evolution: Similar TRSs emerged independently in different SARS-CoV-2 lineages.
The study utilized advanced genetic sequencing and laboratory experiments to analyze the emergence of TRSs. The researchers manipulated the viral genome to observe the impact on viral behavior.
N.iORF3, a truncated protein, disrupts immune signaling by targeting RIG-I, a sensor of viral RNA. The study also identified convergent evolution, indicating that similar TRS patterns may be a common evolutionary strategy among coronaviruses.
The findings have significant public health implications, affecting virus spread and immune response. Continuous monitoring of SARS-CoV-2 evolution is essential for public health strategies and vaccine development.
Future research will explore the molecular mechanisms of N.iORF3 and the broader impact of TRS mutations on the viral genome.
The study was published in PLOS Biology.