Study Overview 
Investigator: O'Connor and Osorio Grant: NIH P51 to WNPRC and NIH R01 supplement 3R01AI116382-01A1S1 to O'Connor


ZIKV-021 tracks data in 34 datasets over 524 time points. Data is present for 2 Participants.

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ZIKV-021 

Primary objectives

The aim of this study is to determine whether fetal outcomes are correlated with the duration of maternal viremia and the extent of ZIKV tissue distribution in fetuses. We will begin this study with a single pregnant macaque. In our other pregnancy studies, we examine viral tissue distribution at specified times following ZIKV infection. We had originally planned to deliver the fetus and perform a necropsy within a week of maternal viremia clearance. We hypothesized that examining fetal tissues close to the time of maternal viremia clearance will best model the full extent of fetal tissue distribution. However, we now know that fetal outcomes, such as head circumference and biparietal diameter, only change later in pregnancy, so we will now deliver the fetus near term.

Study design

One pregnant Indian-origin rhesus macaques will be challenged subcutaneously during week 4 of gestation with 10E4 PFU ZIKV Puerto Rico (PRVABC59) bar code virus. She has a history of DENV3 infection on 3/26/16. Plasma, urine and saliva viral loads will be measured frequently immediately following infection, then twice weekly until plasma viremia has cleared, and then weekly until term. CSF viral loads will be measured twice during pregnancy. We had originally planned to take amniotic fluid samples every other week, amniocentesis were performed a total of three times, but have since decided the procedure is unnecessarily risky and have stopped. The fetus will be delivered near term and undergo necropsy. Over 60 fetal tissues will be examined for ZIKV RNA, histopathology and infectious virus.

Participants

  • 776301 was challenged with 10E4 PFU ZIKV Puerto Rico (PRVABC59) bar code virus on 1.16.17
  • 417332 Fetus of 776301

Clinical and Assay Data

Viral RNA quantification

  • Plasma viral load Chart
  • Pan urine viral load Chart
  • Saliva swab viral load Chart
  • CSF viral load Chart
  • Amniotic fluid viral load Chart

Clinical

  • Animal weights Chart
  • Body Temperature Chart Normal temperature range is between 36 and 40 degrees Celsius.

Immunology

Ultrasound results

-1.10.17 Animal 776301 had her first ultrasound today (day 29 gestation, day -6 prior to infection). Our ultrasonographer measured the crown rump length, saw the yolk sac, measured the gestational sac, saw the placentas and obtained the heart rate. The scan was normal.

-1.17.17 Animal 776301 (gestational day 36, 1dpi) ultrasound had no abnormalities seen

-1.24.17 Animal 776301 (gestational day 43, 8dpi) ultrasound had no abnormalities seen

-1.31.17 Animal 776301 (gestational day 50, 15 dpi) ultrasound had no abnormalities seen

-2.7.17 Animal 776301 (gestational day 57, 22 dpi) First amniocentesis was performed, with viral load in process. Ultrasound had no abnormalities.

-2.14.17 Animal 776301 (gestational day 64, 29 dpi) ultrasound had no abnormalities seen

-2.21.17 Animal 776301 (gestational day 71, 36 dpi) Second amniocentesis was performed and the ultrasound had no abnormalities seen.

-2.28.17 Animal 776301 (gestational day 78, 43 dpi) ultrasound had no abnormalities seen

-3.7.17 Animal 776301 (gestational day 85 , 50 dpi) Third amniocentesis was performed. The ultrasound found that the placenta was calcified along the maternal fetal interface and the intestines were still prominent (subjectively bright along the walls).

-All subsequent weekly ultrasounds on animal 776301: no concerning fetal abnormalities.

Updates

  • 12.21.16 One macaque is in breeding currently.
  • 1.5.17 Animal 776301 is now pregnant and will be challenged on 1.16.17 with Puerto Rican Zika bar code virus.
  • 1.20.17 Mosquito feeding of animal 776301 was performed with uninfected mosquitoes today to determine if viremic monkeys can transmit Zika virus to mosquitoes. Mosquitoes were successfully infected. This is the first feeding of uninfected mosquitoes on infected monkeys that resulted in infection, this animals plasma viremia was also higher during the time of feeding then previous attempts.
  • We had originally planned to take amniotic fluid samples early other week, amniocentesis were performed 22, 36, and 50 DPI, but have since decided the procedure is unnecessarily risky and have stopped. The three amniotic fluid samples that were taken were all negative for viral RNA.
  • Plasma viremia peaked at 5 DPI. Plasma viremia lasted a total of 67 days, making it the second longest viremia we have seen so far in our pregnancy studies. ZIKV-003 currently holds the record at 71 days.
  • The fetus is currently scheduled to be delivered May 16 via cesarean section. The neonate's eyes will be examined and a comprehensive necropsy will be performed.
  • Animal 776301 underwent uneventful delivery of her infant on 5.16.17. The infant had an ocular exam consisting of fundoscopy, slit lamp exam and OCT with no large lesions identified. Over 60 tissues were taken at necropsy and analysis is underway.


Plasma viral load 

Pan urine viral load 

CSF viral load 

Amniotic fluid viral load 

ZIKV neutralizing antibodies 

 

ZIKV neutralizing antibodies 0 and 29 days post infection Data                                            DENV neutralizing antibodies 0 and 29 days post ZIKV infection Data 

Neutralizing antibody data looking at the cross-reactivity of DENV and ZIKV 29 day post ZIKV infection. DENV Data | ZIKV Data

  Attached Files  
   
 ZIKV021_ZIKVPRNT.jpg
 ZIKV-021_DENV_d0_d29_labkey_ids.001.jpeg
 ZIKV-021_DENVandZIKV_29DPI_labkey_ids.001.jpeg


Necropsy tissue viral load: fetus and fetal maternal interface 
FilterGrid ViewsReportsChartsGroupsExportPrintPagingView Specimens
Participant ID
Date
Tissue
vRNA copies / mg
 4173322017-05-16adipose tissue-omentum0.0
4173322017-05-16adrenal gland0.0
4173322017-05-16amniotic/chorionic membrane0.0
4173322017-05-16aorta-thoracic0.0
4173322017-05-16articular cartilage0.0
4173322017-05-16axillary LN0.0
4173322017-05-16bile aspirate0.0
4173322017-05-16bone marrow0.0
4173322017-05-16cerebellum 1 right0.0
4173322017-05-16cerebellum 2 right0.0
4173322017-05-16cerebrum 10 right0.0
4173322017-05-16cerebrum 1 right0.0
4173322017-05-16cerebrum 4 right0.0
4173322017-05-16cerebrum 5 right0.0
4173322017-05-16cerebrum 6 right0.0
4173322017-05-16cerebrum 7 right0.0
4173322017-05-16cerebrum 8 right0.0
4173322017-05-16cervical spinal cord0.0
4173322017-05-16colon0.0
4173322017-05-16cord blood-serum0.0
4173322017-05-16cornea0.0
4173322017-05-16decidua0.0
4173322017-05-16dura mater0.0
4173322017-05-16epidermis/dermis abdomen0.0
4173322017-05-16esophagus0.0
4173322017-05-16eye-aqueous humor0.0
4173322017-05-16femur bone0.0
4173322017-05-16heart0.0
4173322017-05-16inguinal LN0.0
4173322017-05-16jejunum0.0
4173322017-05-16kidney0.0
4173322017-05-16liver0.0
4173322017-05-16lumbar spinal cord0.0
4173322017-05-16lung0.0
4173322017-05-16meconium0.0
4173322017-05-16mesenteric LN 0.0
4173322017-05-16muscle-quadriceps0.0
4173322017-05-16optic nerve0.0
4173322017-05-16ovary0.0
4173322017-05-16pancreas0.0
4173322017-05-16pericardium0.0
4173322017-05-16pituitary gland0.0
4173322017-05-16placental disc 1 0.0
4173322017-05-16placental disc 20.0
4173322017-05-16retina0.0
4173322017-05-16sclera0.0
4173322017-05-16spleen0.0
4173322017-05-16stomach0.0
4173322017-05-16submandibular LN0.0
4173322017-05-16terminal blood draw-plasma0.0
4173322017-05-16terminal CSF0.0
4173322017-05-16thoracic spinal cord0.0
4173322017-05-16thymus0.0
4173322017-05-16thyroid0.0
4173322017-05-16tongue 0.0
4173322017-05-16tonsil0.0
4173322017-05-16tracheobroncial LN0.0
4173322017-05-16umbilical cord0.0
4173322017-05-16urinary bladder0.0
4173322017-05-16urine-aspirate0.0
4173322017-05-16uterus0.0
4173322017-05-16uterus - placental bed 0.0

Biopsy tissue viral load: dam 
FilterGrid ViewsReportsChartsGroupsExportPrintPagingView Specimens
Participant ID
Date
Tissue
vRNA copies / mg
 7763012017-05-16mesenteric LN0.0
7763012017-05-16spleen0.0

Barcode data 

We deep sequenced the barcode region from replicating zika virus in this pregnant animal.  The attached PDF (ZIKV_021_MINIAMPLICONS_forportal.pdf) shows how the analysis of the data was performed using the Zequencer tool.  The raw and processed data can be found linked through the 'MINI amplicon data' list that is located on this page.  

  Attached Files  
   
 ZIKV_021_MINIAMPLICONS_forportal.pdf


Lists 
 MINI amplicon data