Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• The early immunological and virological events establishing Zika virus (ZIKV) infection in humans remain poorly understood.
• Investigating sex-based differences in immune responses to ZIKV is crucial for understanding pathogenesis.

Purpose of the Study:

• To elucidate the early cellular innate immune responses to ZIKV infection in humans.
• To determine the role of these responses in viral persistence and dissemination.
• To identify potential sex differences in ZIKV pathogenesis.

Main Methods:

• Analysis of early cellular innate immune responses in blood and tissues following ZIKV infection.
• Quantification of immune cell recruitment, including plasmacytoid dendritic cells and monocytes.
• Measurement of cytokine production, specifically monocyte chemoattractant protein (MCP-1).
• Identification of primary in vivo ZIKV target cells in blood and lymph nodes.

Main Results:

• Robust early cellular innate immune responses to ZIKV were observed in blood and tissues.
• These responses were significantly stronger in males and correlated with increased viral persistence.
• Early recruitment of plasmacytoid dendritic cells and higher MCP-1 production were associated with greater viral persistence and tissue dissemination.
• Non-classical monocytes were identified as primary in vivo targets of ZIKV in the blood and peripheral lymph node.

Conclusions:

• Early cellular innate immune responses in the blood play a key role in ZIKV dissemination and pathogenesis.
• Significant sex differences exist in ZIKV pathogenesis, with stronger immune responses in males correlating with increased viral persistence.
• Non-classical monocytes are identified as critical cellular targets for ZIKV in vivo.