Newswise — In a groundbreaking study set to be published on June 8th in the open access journal PLOS Biology, researchers led by Matthew D. Daugherty from the University of California, United States, have shed light on the crucial role of molecular sensors known as the "inflammasome" in activating inflammatory responses against pathogens. The study reveals that one particular sensor, CARD8, has undergone significant evolutionary advancements, enabling it to detect various types of viruses and play a vital role in the human immune system's ability to sense and mount a response against coronavirus infections.

Unraveling the mechanisms behind pathogen detection is crucial for understanding the activation of immune responses in the human body. However, the specific mechanisms involved in this detection process have remained elusive. To shed light on the evolutionary adaptations of CARD8 in sensing viral infections, the team of researchers conducted a comprehensive series of experiments utilizing human cell lines. These experiments aimed to investigate how CARD8 responds to various viruses. Additionally, the researchers analyzed genetic variations of CARD8 across different mammalian species and within the human population. By combining these approaches, the study aimed to gain insights into the evolutionary history and functional significance of CARD8 in the context of pathogen detection.

The study's findings demonstrated the indispensable role of CARD8 in initiating an effective immune response against coronavirus infections. Furthermore, the researchers discovered that CARD8 possesses the capability to detect viral enzymes from a minimum of three distinct virus families, including the Coronaviridae family to which coronaviruses belong. Notably, CARD8 has undergone significant evolutionary changes across various mammalian species. Additionally, variations in CARD8 were observed among different individuals within the human population.

While these findings provide valuable insights into CARD8's evolutionary and functional aspects, further research is warranted to comprehend how reservoir species of viral pathogens, such as bats in the case of coronaviruses, respond to viral infections. It remains intriguing that bats, acting as a reservoir for coronaviruses, either lack CARD8 sensors or possess a version of CARD8 that is incapable of responding to the viral enzymes associated with coronaviruses. Future investigations will shed light on the mechanisms and adaptations in reservoir species that enable them to host viral pathogens.

According to the researchers, the study's findings solidify the role of CARD8 as a dynamic and diverse innate immune sensor for positive-sense RNA viruses. The research demonstrates that CARD8 possesses the ability to detect viral proteases derived from at least three different viral families, which encompass significant human pathogens like Coronaviridae, Picornaviridae, and Retroviridae. The evolutionary and functional analyses conducted in the study emphasize that sequence variations in CARD8 among different species and within the human population significantly influence its capacity to recognize and respond to viral proteases. These discoveries highlight the remarkable adaptability and importance of CARD8 as a critical component of the immune system's defense against a broad range of viral infections.

In an intriguing observation, Daugherty remarks, "This research reveals a captivating mechanism through which the human immune system has evolved to detect and mount a response against coronavirus infections, including SARS-CoV-2." What makes it even more intriguing is the genetic variation identified in certain individuals that renders them less capable of sensing and responding to coronavirus infections. However, this genetic difference provides them with an enhanced ability to respond to infections caused by other viruses, such as human rhinovirus, commonly known as the 'common cold' virus. This underscores the complex interplay between genetic variations, viral infections, and immune responses, highlighting the diverse ways in which the immune system can adapt and specialize in its defense against different pathogens.


Journal Link: PLOS Biology