Fetal Zika virus inoculation in macaques revealed control of the fetal viral load during pregnancy

• Published in: Virology journal Vol. 21; no. 1; pp. 209 - 15
• Main Authors: Egloff, Charles, Fovet, Claire-Maëlle, Denis, Jessica, Pascal, Quentin, Bossevot, Laetitia, Luccantoni, Sophie, Leonec, Marco, Dereuddre-Bosquet, Nathalie, Leparc-Goffart, Isabelle, Le Grand, Roger, Durand, Guillaume André, Badaut, Cyril, Picone, Olivier, Roques, Pierre
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 03.09.2024; BioMed Central; BMC
• Subjects: Brain; Brain damage; Cesarean section; Development and progression; Ethylenediaminetetraacetic acid; Fetus; Growth; Infection; Injuries; Microcephaly; Neutralizing antibodies; Nonhuman primate model; Pregnant women; RNA; TORCH infection; Ultrasound imaging; Viral clearance; Zika virus; France
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-024-02468-x

Early pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6-5.0% of cases, but the underlying mechanisms remain largely unknown. To understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 10.sup.3 PFU of ZIKV at 70-80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group). ZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced. ZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.