The JAK-STAT pathway in invertebrates: An emerging battleground for host‒virus warfare

The arms race between hosts and viruses for dominance over the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway has been extensively studied in vertebrates but remains poorly explored in invertebrates. Recent studies have revealed that the antiviral Vago/JAK-STAT pathway in invertebrates operates as a parallel mechanism to the vertebrate interferon (IFN)/JAK-STAT pathway, suggesting a highly conserved antiviral mechanism across the animal kingdom. Moreover, invertebrates appear to employ multifaceted strategies to modulate the JAK-STAT pathway to inhibit viral replication or enhance host tolerance, while viruses can counteract by manipulating the JAK-STAT pathway to their advantage. Thus, the competition between hosts and viruses for control of the JAK-STAT pathway also exists in invertebrates, indicating this arms race is also conserved in evolution. This review summarizes the discovery of the Vago/JAK-STAT pathway, its comparison to the IFN/JAK-STAT pathway, and the mechanisms underlying the host-virus tug-of-war over the JAK-STAT pathway in invertebrates. These insights shed light on this highly conserved immune strategy, its implication for host-virus interaction, and its potential application in disease control.