Molecular sensors that form the so-called inflammasome help activate inflammatory responses to pathogens. A new study suggested that CARD8 is a highly evolved sensor that can detect a variety of viruses and is critical to the human immune system's capacity to identify and respond to coronavirus infection.
The findings of the study were published in the open-access journal PLOS Biology by Matthew D. Daugherty at the University of California, United States and colleagues.
The human body must first recognise a pathogen in order to trigger an immunological response. These detecting techniques, however, remain unclear. Researchers employed human cell lines in a series of studies to explore how CARD8 responds to different viruses in order to understand how it developed to recognise viral infections. They also looked at CARD8 genetic variation in mammals and humans.
CARD8 is essential for an immune response to coronavirus infection and can identify viral enzymes from at least three distinct virus families, including Coronaviridae, according to the researchers. CARD8 has evolved significantly across diverse mammalian species and varies amongst human individuals.
However, further research is needed to understand how reservoir species of viral diseases may respond to viral infections. Bats, for example, are a coronavirus reservoir but lack CARD8 sensors or have a form of CARD8 that does not respond to 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 added, "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)." (ANI)