Transmission electron micrograph of vesicular stomatitis virus (VSV) particles (teal) found in extracellular space and budding from the plasma membrane of infected cells (purple). Image captured at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Image credit: NIAID (CC BY 2.0)
Before the immune system can eliminate a bacterium, virus or other type of pathogen, it needs to be able to recognize these foreign elements. To achieve this, cells in the immune system have proteins called pattern recognition receptors (PRRs) which can identify distinct molecular features of certain pathogens.
One specific group of PRRs is a family of retinoic acid-induced RIG-I-like receptors (RLRs), which help immune cells detect different types of viruses. Members of this family recognize distinct motifs on the genetic material of viruses known as RNA. For instance, RIG-I recognizes a marker known as 5’ppp on the end of single-stranded RNA molecules, whereas MDA5 recognizes long strands of double-stranded RNA.
Many vertebrates – including various mammals, birds, and fish – lost the RIG-I receptor over the course of evolution. However, Geng et al. predicted that some animals lacking the RIG-I receptor may still be able to activate an immune response against viruses that contain the 5’ppp-RNA motif.
To investigate this possibility, Geng et al. studied chickens and miiuy croakers (a type of ray-finned fish) which no longer have a RIG-I receptor. They found that both animals can still sense and eliminate two 5’ppp-RNA viruses called VSV and SCRV. Further experiments revealed that these two viruses are detected by a modified MDA5 receptor that had evolved to bind to 5’-ppp and activate the antiviral response.
Viruses are also continuously evolving new ways to escape the immune system. This led Geng et al. to investigate whether SCRV, which causes serious harm to marine fish, has evolved a way to evade the MDA5 protection mechanism. Using miiuy croakers as a model, they found that SCRV causes the transcripts that produce the MDA5 protein to contain more molecules of m6a. This molecular tag degrades the transcript, leading to lower levels of MDA5, reducing the antiviral response against SCRV.
The findings of Geng et al. offer valuable perspectives on how the immune system adapts over the course of evolution, and highlight the diversity of antiviral responses in vertebrates. Chickens and miiuy croakers are commonly farmed animals, and further work investigating how viruses invade these species could prevent illnesses from spreading and having a negative impact on the economy.
