WSV403 suppresses JAK/STAT signaling to impair antiviral resistance in Pacific white shrimp Penaeus vannamei

Viral immediate early (IE) genes are key regulators of host antiviral defenses. White spot syndrome virus (WSSV) IE gene WSV403 encodes an E3 ligase which regulates the latency state of WSSV. However, the role of WSV403 in host immune response remains unclear. Here, we generated a transgenic Drosophila line that overexpresses WSV403 and found that WSV403 suppresses the JAK/STAT pathway and its downstream genes, leading to increased susceptibility and viral load upon Drosophila C virus infection. We further showed that WSV403 suppresses Stat92E expression without affecting its phosphorylation or degradation, suggesting a novel mechanism of JAK/STAT inhibition. Moreover, we demonstrated that knockdown of WSV403 in the Pacific white shrimp Penaeus vannamei reduces WSSV replication and enhances transcript levels of JAK/STAT pathway components. Our results revealed the immune modulatory function of WSV403 and uncovered a new mechanism by which WSSV inhibits host JAK/STAT signaling to impair antiviral resistance against WSSV infection.