CARD8 Inflammasome Found to Be Versatile Viral Detector

Inflammasomes, complex molecular sensors that activate immune responses during infections, have long fascinated immunologists due to their intricate mechanisms. Now University of California San Diego researchers have uncovered a new way in which the immune system detects certain viruses. In a study published in PLOS Biology, they found that the inflammasome protein CARD8 can act as a trip wire, detecting a range of viruses, including SARS-CoV-2.

The research, led by Matthew Daugherty, along with colleagues from the University of Washington and UC Berkeley, revealed that CARD8 functions differently among species and even varies among individuals within the human population. By conducting experiments on human cell lines and analyzing genetic variation in CARD8 across mammalian species, they discovered that some humans have lost the ability to sense coronavirus infections due to a single genetic difference. However, they have gained the ability to sense viruses in a different family, such as the common cold and poliovirus.

Interestingly, the researchers found that the bat version of CARD8 is unable to sense coronaviruses. This sheds light on how coronaviruses can easily infect bats and become a viral reservoir. The study's findings demonstrate that CARD8 has evolved significantly across different mammalian species and within individual humans, establishing it as a rapidly evolving innate immune sensor of positive-sense RNA viruses. However, the researchers believe they have only scratched the surface in understanding how immune sensors alert the body to pathogens and infections.

Further research is needed to fully comprehend the role of CARD8 in the severity of COVID-19 infections and long-term symptoms. The researchers speculate that diminished CARD8 inflammasome activation could contribute to variations in COVID-19 disease outcomes and potentially affect other human pathogenic coronavirus and picornavirus infections. The study's findings provide valuable insights into the diverse functionality of CARD8 and highlight the complex interplay between the immune system and viral infections.