Certain individuals have genetically lost the ability to detect coronavirus infections via the recently discovered CARD8 sensor.
Inflammasomes constitute a complex network of molecular alarms that are triggered in our bodies upon the onset of an infection. Yet, the inner workings of these sensors, responsible for kick-starting defenses against threats such as harmful pathogens, have piqued the curiosity of immunologists due to their intricate operational mechanisms.
In a new study, University of California San Diego biologists describe a previously unknown way that the immune system detects certain viruses. The inflammasome immune protein known as CARD8, they found, can serve as a trip wire to detect a range of viruses, including SARS-Cov-2, which causes
Adding a twist to their discovery, researchers led by the School of Biological Sciences’ Matt Daugherty and colleagues at the “In a version of CARD8, we found that some humans have lost the ability to sense coronavirus infections based on a single genetic difference but have gained the ability to sense viruses in a different family, the enteroviruses—which includes rhinovirus (common cold) and poliovirus,” said Daugherty, an associate professor in the Department of Molecular Biology. “So that means it’s an evolutionary tradeoff and CARD8 diversity in humans impacts which viruses can be sensed and which ones cannot.”
The research team found that the bat version of CARD8 is not able to sense coronaviruses. This could explain how coronaviruses are able to infect bats so easily and become a
The findings provide evidence that CARD8 has evolved substantially across different species of mammals and individual humans. According to the authors, “Our findings establish CARD8 as a rapidly evolving, polymorphic, innate immune sensor of positive-sense
More studies are needed to thoroughly determine CARD8’s role in the severity of COVID-19 infections and long COVID symptoms.
“It is tempting to speculate that diminished CARD8 inflammasome activation may be a contributing factor to variation in COVID-19 disease outcomes, and more generally for other human pathogenic coronavirus and picornavirus infections,” the authors note.
Reference: “Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome” by Brian V. Tsu, Rimjhim Agarwal, Nandan S. Gokhale, Jessie Kulsuptrakul, Andrew P. Ryan, Elizabeth J. Fay, Lennice K. Castro, Christopher Beierschmitt, Christina Yap, Elizabeth A. Turcotte, Sofia E. Delgado-Rodriguez, Russell E. Vance, Jennifer L. Hyde, Ram Savan, Patrick S. Mitchell and Matthew D. Daugherty, 8 June 2023, PLOS Biology.
DOI: 10.1371/journal.pbio.3002144
The study was funded by the