Scientists at the University of California San Diego have made a groundbreaking discovery regarding the immune system’s ability to detect specific viruses, including SARS-CoV-2, by means of an immune protein called CARD8. However, the function of CARD8 varies among species and individuals, influencing its capacity to identify different viruses and potentially contributing to the variability observed in COVID-19 disease outcomes.
A subset of individuals has genetically lost the capability to detect coronavirus infections through the recently revealed CARD8 sensor.
Inflammasomes constitute a complex network of molecular alarms that our bodies activate upon encountering an infection. The intricate mechanisms behind these sensors, responsible for initiating defenses against harmful pathogens, have captured the attention of immunologists.
In a recent study, biologists from the University of California San Diego unveiled a previously unknown method by which the immune system identifies specific viruses. They discovered that the inflammasome immune protein CARD8 can act as a trip wire, detecting a range of viruses, including SARS-CoV-2, the virus responsible for COVID-19.
Adding a fascinating twist to their findings, researchers led by Matt Daugherty from the School of Biological Sciences, along with colleagues from the University of Washington and UC Berkeley, determined that CARD8 functions differently across various species and even among individuals within the human population. These findings, resulting from experiments conducted on human cell lines and an analysis of CARD8 genetic variation in mammalian species, are detailed in the journal PLOS Biology.
“In one variant of CARD8, we observed that certain humans have lost the ability to detect coronavirus infections due to a single genetic difference, but they have gained the ability to sense viruses from a different family, namely the enteroviruses, which include rhinovirus (common cold) and poliovirus,” explained Daugherty, an associate professor in the Department of Molecular Biology. “This evolutionary tradeoff indicates that CARD8 diversity in humans affects the viruses that can be sensed and those that cannot.”
The research team discovered that the bat version of CARD8 is incapable of detecting coronaviruses. This may explain why coronaviruses can infect bats so easily, making bats a reservoir for these viruses.
The findings provide evidence that CARD8 has undergone substantial evolution across different mammalian species and individual humans. As the authors state, “Our findings establish CARD8 as a rapidly evolving, polymorphic, innate immune sensor of positive-sense RNA viruses.”
Daugherty mentioned that researchers have only scratched the surface in understanding how immune sensors signal the presence of pathogens and infections.
“The incredible balance between sensing and not sensing different viruses and its evolutionary implications are truly mind-blowing,” expressed Daugherty.
Further studies are necessary to thoroughly investigate the role of CARD8 in the severity of COVID-19 infections and long-term symptoms.
“It is tempting to speculate that reduced CARD8 inflammasome activation may contribute to variations in COVID-19 disease outcomes, as well as 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.
The study received funding from the National Institutes of Health, the Pew Biomedical Scholars Program, the Hellman Fellows Program, the Burroughs Wellcome Fund, the Helen Hay Whitney Foundation, the Ford Foundation Predoctoral Fellowship Program, the National Science Foundation Graduate Research Fellowship, the Mallinckrodt Foundation, the UC Berkeley CEND Catalyst award, and the Howard Hughes Medical Institute.
The research study was authored by Brian Tsu, Rimjhim Agarwal, Nandan Gokhale, Jessie Kulsuptrakul, Andrew Ryan, Elizabeth Fay, Lennice Castro, Christopher Beierschmitt, Christina Yap, Elizabeth Turcotte, Sofia Delgado-Rodriguez, Russell Vance, Jennifer Hyde, Ram Savan, Patrick Mitchell, and Matthew Daugherty.
Frequently Asked Questions (FAQs) about immune protein CARD8
What did scientists discover about the immune system’s detection of viruses like SARS-CoV-2?
Scientists from the University of California San Diego discovered that the immune protein CARD8 serves as a versatile “trip wire” that can detect various viruses, including SARS-CoV-2, the virus responsible for COVID-19. The function of CARD8 varies among species and individuals, which may contribute to the variation in COVID-19 disease outcomes.
How does the genetic variation in CARD8 affect virus detection?
Genetic variation in CARD8 influences its ability to sense different viruses. Some individuals have lost the ability to detect coronavirus infections through the CARD8 sensor due to a single genetic difference. However, they have gained the ability to sense viruses from a different family, such as the enteroviruses (rhinovirus and poliovirus). This indicates an evolutionary tradeoff in CARD8 diversity among humans.
Why is the discovery of CARD8’s role significant?
The discovery of CARD8 as a versatile immune protein sheds light on the mechanisms by which the immune system detects and responds to viral infections. It provides insights into the intricate workings of inflammasomes, the molecular alarms that trigger our body’s defenses against pathogens. Understanding CARD8’s function and variation can have implications for COVID-19 disease outcomes and the evolution of viruses.
How does CARD8’s variation impact different species?
The research findings indicate that CARD8 has evolved substantially across different species of mammals. For example, the bat version of CARD8 is unable to detect coronaviruses, potentially explaining why bats can be easily infected and serve as a reservoir for these viruses. The study highlights the diverse functions of CARD8 among various species and its role in viral sensing.
The research suggests that the variation in CARD8 inflammasome activation could be a contributing factor to the variation observed in COVID-19 disease outcomes. Additionally, it raises the possibility that CARD8 may play a role in the severity of other human pathogenic coronavirus and picornavirus infections. Further studies are needed to thoroughly investigate CARD8’s involvement and potential therapeutic implications for these viral infections.