# Hijacking of host Src-PI3K-Akt signaling by WSSV IE1 protein suppresses apoptotic and autophagic defenses to facilitate viral proliferation

## TL;DR

This study shows how a virus hijacks a host cell's signaling pathway to block defenses and help itself multiply.

## Contribution

The study reveals a novel mechanism by which WSSV uses the Src-PI3K-Akt pathway to suppress apoptosis and autophagy.

## Key findings

- WSSV infection activates the PI3K-Akt pathway early in Penaeus vannamei.
- The IE1 protein interacts with Src64B kinase to trigger PI3K-Akt signaling.
- Activation of this pathway suppresses host defenses, aiding viral proliferation.

## Abstract

The phosphoinositide 3-kinase (PI3K)-Akt pathway is a key signaling cascade regulating diverse cellular processes, including proliferation, survival, autophagy, translation, and metabolism. White spot syndrome virus (WSSV), a major pathogen devastating global crustacean aquaculture, has been demonstrated to exploit the PI3K-Akt pathway to facilitate its proliferation. However, the precise mechanism underlying this viral modulation remained unclear. In this study, we demonstrate that WSSV infection induces activation of the PI3K-Akt pathway during the early infection stage in Penaeus vannamei. Mechanistically, we reveal that the WSSV immediate-early protein IE1 interacts with and activates host Src64B kinase via its Y129FTS tyrosine motif. This specific interaction promotes recruitment of the PI3K regulatory subunit alpha (PI3Kp85α), thereby triggering the downstream PI3K-Akt signaling. By activating this pathway, WSSV establishes a favorable environment for its proliferation by suppressing host apoptotic and autophagic defenses. Our findings unveil a previously unknown mechanism of WSSV immune evasion through Src-PI3K-Akt signaling hijacking and identify components of this signaling hub as potential therapeutic targets for anti-WSSV strategies.

Viruses usually hijack host signaling pathways to enhance infectivity and evade immune defenses. Understanding these interactions is critical for elucidating viral pathogenesis and developing effective antiviral strategies. Here, we demonstrate that the WSSV immediate-early protein IE1 binds to and activates host Src64B kinase, which in turn recruits PI3Kp85α and activates the PI3K-Akt signaling cascade. Activation of this pathway suppresses apoptosis and autophagy, thereby facilitating viral proliferation. These findings advance our understanding of WSSV pathogenesis and identify the Src-PI3K-Akt signaling as a promising therapeutic target for anti-WSSV intervention.