Zika Virus Infection Is More Highly Replicative and Transmissible by Extracellular Vesicles in Human than in Mouse...

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Zika virus (ZIKV) causes neurological disorders in humans.
• Mechanisms of ZIKV neuronal infection and antiviral responses are unclear.

Purpose of the Study:

• To investigate ZIKV infection dynamics in human and mouse neuronal cells.
• To explore the role of extracellular vesicles (EVs) in ZIKV transmission.
• To analyze ZIKV-induced changes in neuronal antiviral responses.

Main Methods:

• Infection of human SH-SY5Y and mouse N2a/cortical neurons with ZIKV.
• Quantification of viral loads and EV secretion.
• Analysis of type 1 interferon (IFN) and TAM receptor expression.

Main Results:

• Human neuronal cells exhibited higher ZIKV loads than mouse cells.
• Infectious EVs enhanced ZIKV infection in all tested neuronal types.
• ZIKV infection upregulated EVs, IFN-beta, and TAM receptors in human neurons.
• Mouse neurons showed restricted viral replication and reduced IFN expression.

Conclusions:

• Human neurons are more susceptible to ZIKV infection than murine neurons.
• EV-mediated transmission contributes to ZIKV neurotropism.
• Murine cells possess intrinsic mechanisms to limit ZIKV replication, explaining lack of mouse models.
• Differential neuronal susceptibility may underlie ZIKV-induced microcephaly.