Molecular sensors that form the so-called “inflammasome” help activate inflammatory responses to pathogens. A study publishing June 8th in the open access journal PLOS Biology by Matthew D. Daugherty at University of California, United States and colleagues suggests that the sensor CARD8 is highly evolved, can detect a range of viruses, and is important to the human immune system’s ability to sense and respond to coronavirus infection.
In order to activate an immune response, the human body must first detect a pathogen. However, these detection mechanisms remain unclear. In order to understand how CARD8 has evolved to sense viral infections, researchers used a series of experiments using human cell lines, testing how CARD8 responds to different viruses. They also analyzed CARD8 genetic variation across mammalian species and in humans.
The researchers found that CARD8 is required for an immune response to coronavirus infection and can detect viral enzymes from at least three different families of viruses, including Coronaviridae. CARD8 has evolved substantially across different species of mammals and is different among different human individuals. Future studies are needed, however, to understand how reservoir species of viral pathogens may respond to viral infections. Bats, for example, are a coronavirus reservoir, but either do not have CARD8 sensors or have a version of CARD8 that cannot respond to the coronavirus enzymes.
According to the authors, “Our findings establish CARD8 as a rapidly evolving, polymorphic, innate immune sensor of positive-sense RNA viruses. We demonstrate that CARD8 has the capacity to detect viral proteases from at least three viral families that include important human pathogens: Coronaviridae, Picornaviridae, and Retroviridae. Our evolutionary and functional studies further indicate that CARD8 sequence variation between species and within humans has a profound impact on the ability to sense viral proteases.”
Daugherty adds, “This is a fascinating way that the human immune system has evolved to detect and respond to infection by coronaviruses, including SARS-CoV-2. Even more interesting, a genetic difference in some humans makes them less able to sense and respond to coronavirus infections, but gives them increased ability to respond to infections by other viruses, including human rhinovirus (i.e., the ‘common cold’ virus).”
Journal Reference:
- Tsu BV, Agarwal R, Gokhale NS, Kulsuptrakul J, Ryan AP, Fay EJ, et al. (2023) Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. PLoS Biol 21(6): e3002144. DOI: 10.1371/journal.pbio.3002144