Unzipping the C. elegans immune response to viral infection

BioTechniques News
Aisha Al-Janabi

The zip-1 gene in the worm Caenorhabditis elegans (C. elegans) has been identified as the central hub for immune response – providing new avenues for research into human immunity against viruses. 

Researchers from University of California San Diego  have discovered that the zip-1 gene, encoding the ZIP-1 protein transcription factor controlling gene activation, is responsible for the first-line immune response in C. elegans. Led by Vladimir Lažetić, the study revealed that ZIP-1 acts as a central hub for immune response against infectious threats. The findings establish a foundation for identifying similar genes that control the immune response in humans.

C. elegans is a commonly utilized model for studying infection as its transparent body allows close monitoring in the lab. The researchers investigated the worms’ immune response to triggers including heat stress, proteasome inhibition, viral (Orsay) and fungal (microsporidia) infections. The team used a fluorescence and bioluminescence tracking methods to identify cellular pathways involved in the worms’ immune response to infection, demonstrating that zip-1 is an intracellular pathogen response regulator to all the tested triggers. 

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The team found this surprising as, despite the molecular differences of the viral and fungal pathogens, they both induced a zip-1 regulated immune response – demonstrating zip-1 is a central hub for immune defense. “A virus, a fungus and heat stress are all so different, but we found that they’re all going through the same central ZIP-1 hub to turn on a set of immune genes,” senior author Emily Troemel noted. 

“We also observed that ZIP-1 is activated by a previously described receptor that is important for triggering antiviral immunity, both in mammals and in C. elegans, so there are links that can be made with human immunity,” Lažetić explained. “The new antiviral factor that we’ve identified is giving us a better handle on immunity and how worms are fighting off viral infections. Worms sense an RNA virus in a way that’s similar to how humans sense an RNA virus like coronavirus,” Troemel added. 

Linking the involvement of ZIP-1 in C. elegans immune response could be important for further unraveling how humans confer immunity against viruses. 

“Understanding the early role of ZIP-1 is important because we know that timing matters so much in terms of immune response. That’s one of the lessons we have learned with COVID. If you have an early interferon response, that tends to correlate very well with fighting off the infection,” Troemel explained. 

Interactions between the cellular receptors detecting infection and the activation of ZIP-1 are being further explored as these receptors are known to be similar to those in the human immune response. 

“Revolutions in biology oftentimes have come from understanding how simple organisms cope with threats such as infection,” highlighted Troemel. “Studies that might seem abstract can lead to groundbreaking discoveries.” 

The post Unzipping the <em>C. elegans</em> immune response to viral infection appeared first on BioTechniques.

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