Zika Virus NS1 Hijacks Mitochondria Through Tunneling Nanotubes for Immune Evasion
The study titled “Zika virus NS1 drives tunneling nanotube formation for mitochondrial transfer and stealth transmission in trophoblasts” (Nature Communications, February 2025), published by Dr. Indira Mysorekar and her team, explores how Zika virus (ZIKV) utilizes a stealth mechanism to spread among placental trophoblasts. The research focuses on the role of the viral protein NS1 in facilitating this process.
Key Findings:
- Tunneling Nanotube Formation: ZIKV induces the formation of tunneling nanotubes (TNTs) in placental trophoblasts, which serve as conduits for transferring viral components and mitochondria to neighboring uninfected cells.
- Role of NS1 Protein: The non-structural protein 1 (NS1) of ZIKV, particularly its N-terminal 1–50 amino acids, is critical for triggering TNT formation in host cells.
- Immune Evasion: Trophoblasts infected with a TNT-deficient ZIKV mutant elicited a stronger antiviral interferon response compared to those infected with wild-type ZIKV, suggesting that TNT-mediated transmission helps the virus evade host immune defenses.
- Mitochondrial Hijacking: ZIKV infection or NS1 expression leads to increased mitochondrial levels in trophoblasts, with mitochondria being transferred via TNTs from healthy to infected cells, potentially supporting viral replication and survival.
These findings shed light on a novel mechanism by which ZIKV spreads and evades the immune system, offering potential targets for therapeutic intervention.
