Iron availability affects West Nile virus infection in its mosquito vector

Area of Science:

• Vector-borne diseases
• Insect molecular biology
• Virology

Background:

• Mosquitoes transmit viruses like dengue and West Nile virus.
• Female mosquitoes require blood meals, exposing them to high iron levels.
• Iron is vital for pathogen replication, and hosts sequester it as a defense.

Purpose of the Study:

• To investigate the impact of iron availability on viral replication in mosquitoes.
• To understand mosquito cellular responses to viral infection concerning iron homeostasis.

Main Methods:

• Culex mosquito cells were treated with iron (ferric ammonium citrate) or an iron chelator (deferoxamine).
• Gene expression of ferritin and NRAMP (an iron transporter) was analyzed.
• NRAMP gene knockdown and mosquito infection models were used to validate findings.

Main Results:

• Viral infection increased ferritin and NRAMP mRNA levels in mosquito cells.
• Increased iron levels correlated with higher viral titers.
• Reducing intracellular iron via NRAMP knockdown or deferoxamine treatment decreased viral titers in cells and mosquitoes.
• Deferoxamine treatment reduced viral loads in mosquito midgut, carcass, and saliva, decreasing transmission capacity.

Conclusions:

• Iron is necessary for efficient viral replication within mosquito cells.
• Mosquitoes upregulate ferritin to sequester iron, limiting its availability to viruses.
• Ferritin likely plays a role in the mosquito's innate immune response against viral infections.