Preliminary Studies on Immune Response and Viral Pathogenesis of Zika Virus in Rhesus Macaques

Area of Science:

• Virology
• Immunology
• Primate Models

Background:

• Zika virus (ZIKV) poses a significant public health threat, primarily transmitted by mosquitoes but also sexually and vertically.
• Understanding ZIKV's systemic pathology and immune response based on transmission route is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate ZIKV's systemic infection, persistence, and associated immune responses in rhesus macaques (RMs) following intravaginal (IVAG) versus subcutaneous (sub Q) inoculation.
• To explore potential route-specific differences in ZIKV pathology and immune cell modulation.

Main Methods:

• Rhesus macaques were inoculated with ZIKV (PRVABC59) via IVAG (n=3) or sub Q (n=2) routes.
• Systemic infection was monitored, and viral presence in plasma and various anatomical sites, including the brain, was assessed up to 60 days postinfection (dpi).
• Immune cell populations (CD11C hi myeloid cells, NK cells, CD8+ central memory cells) were analyzed to identify route-specific changes.

Main Results:

• Systemic ZIKV infection was confirmed in all RMs irrespective of the inoculation route.
• ZIKV persisted in multiple anatomical locations, including brain regions, up to 60 dpi.
• IVAG ZIKV infection was associated with distinct immune cell changes compared to sub Q infection, including CD11C hi myeloid cell depletion and altered NK and CD8+ T cell populations.

Conclusions:

• ZIKV infection appears to be systemic and persistent, regardless of whether it is introduced via IVAG or sub Q routes in rhesus macaques.
• Route of ZIKV inoculation influences specific immune cell responses, highlighting potential differences in pathogenesis.
• Further research with larger animal cohorts is warranted to validate these preliminary findings on ZIKV transmission routes and immune modulation.