We will test the hypothesis that the risk of fetal injury due to Zika virus infection is proportional to the amount of virus present. This question is of great importance to the field as a whole, if this hypothesis is correct we hope to provide the basis for a model of microcephaly by establishing a dose of Zika virus that is likely to result in microcephaly. We will follow fetal development closely, looking for signs of microcephaly or fetal injury similar to microcephaly.
Two pregnant Indian-origin rhesus macaques will be infected with a high dose of ZIKV Puerto Rico (PRVABC59) around gestational day 45. The animals will be inoculated with 5 subcutaneous doses of 10e7 PFU of virus. Plasma, urine and saliva viral loads will be measured frequently immediately following infection, then biweekly for the duration of positive plasma viremia, and then weekly throughout pregnancy. The fetus will be monitored by weekly by ultrasound.
Clinical and Assay Data
Viral RNA Quantification
- Plasma viral load Chart
- Pan urine viral load Chart
- Oral swab viral load Chart
May 2, 2017: Participant 125500 was challenged with five subcutaneous doses of 10e7 PFU of ZIKV Puerto Rico (three injections into the left forearm and two in the right) at 50 days of gestation.
- Peak viral load was reached at 2 DPI with a plasma viral load of 6.6e7.
- Plasma viremia was resolved by 24 DPI, with the last positive plasma viral at 21 DPI.
- Currently, the fetus is scheduled to be delivered via c-section August 15, 2016.
- August 15, 2017: Fetus 411377 was scheduled to be delivered by C-section today. The fetus was stillborn. Gross analysis suggests intrauterine death within the last few days. The fetus appeared normal at delivery and ultrasound was unremarkable when performed 7 days ago. This is the second instance of fetal death we have observed following maternal infection with PRVABC59, the other was described here
- On the day of the C-section bacterial cultures were taken from the following fetal and maternal-fetal interface sites: lung, liver, spleen, stomach, umbilicus tissue, amniotic fluid, placenta, and uterine tissue. All bacterial cultures were negative.
- Ocular histology for the still born fetus 411377 results came back with no defects noted beyond the expected moderate to severe autolysis. The full pathology report can be read here.