Evaluation of Viral Replication by Tonate Virus (TONV) and Zika Virus (ZIKV), Within an ex Vivo Trophoblast and Placental Model

• Conditions: Zika Virus Infection
• Interventions: Biological: Cell line and virus; Biological: Infection of human placental culture explants; Biological: Determination of viral load in tissues by qRT-PCR

• Registration Number: NCT05589012
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Prospective, non-interventional study carried out after culturing placental trophoblastic tissue ex vivo and infection with Zika and Tonate

Detailed Description

The analysis will relate for each virus studied + control + favipiravir to 1 placenta in the 1st trimester and 1 placenta at term.

2 experiments per virus will be planned.

Study Timeline

• Status Verified: 2022-08
• Study First Submitted: 2022-08-22
• Study First Submitted QC: 2022-10-17
• Last Update Submitted: 2022-10-17
• Study First Posted: 2022-10-21
• Last Update Posted: 2022-10-21
• Study Start: 2023-11-01
• Primary Completion: 2024-04-01
• Study Completion: 2024-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 8

Inclusion Criteria

• Patient over 18 years old
• Singleton pregnancy of normal course, at term, birth by caesarean section OR
• Trophoblast from Voluntary Termination of Pregnancy (IVG), after endo-uterine aspiration

Exclusion Criteria

• Need for pathological, genetic or bacteriological examination of the placenta
• Multiple pregnancy
• HBV+ (Hepatitis B positive), HCV+ (Hepatitis C positive) , known CMV seroconversion during pregnancy (CytoMégaloVirus)
• Immunosuppression (drugs, corticosteroids, etc.)
• Diabetes
• Pre eclampsia
• Intrauterine growth retardation (IUGR),
• Vascular or placental pathology.
• Refusal to participate
• Patient under guardianship / curatorship / security measure
• Patient under AME (state medical aid)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Human placentas and trophoblasts (biological waste) from uncomplicated pregnancies.	Cell line and virus	The placentas will be collected following a birth by caesarean section after oral and written information by delivery of the information note for women who have had a normal singleton pregnancy at term. Similarly, trophoblasts are collected following endo-uterine aspiration in the context of voluntary termination of pregnancy. * Cell line and virus * Infection of human placental culture explants * Determination of viral load in tissues by qRT-PCR
Human placentas and trophoblasts (biological waste) from uncomplicated pregnancies.	Determination of viral load in tissues by qRT-PCR	The placentas will be collected following a birth by caesarean section after oral and written information by delivery of the information note for women who have had a normal singleton pregnancy at term. Similarly, trophoblasts are collected following endo-uterine aspiration in the context of voluntary termination of pregnancy. * Cell line and virus * Infection of human placental culture explants * Determination of viral load in tissues by qRT-PCR
Human placentas and trophoblasts (biological waste) from uncomplicated pregnancies.	Infection of human placental culture explants	The placentas will be collected following a birth by caesarean section after oral and written information by delivery of the information note for women who have had a normal singleton pregnancy at term. Similarly, trophoblasts are collected following endo-uterine aspiration in the context of voluntary termination of pregnancy. * Cell line and virus * Infection of human placental culture explants * Determination of viral load in tissues by qRT-PCR

Primary Outcome Measures

Name	Time	Method
To assess the replication potential of TONV and ZIKV after placenta infection ex vivo.	inclusion	Determine the viral load (RT-qtPCR) of TONV and ZIKV after placenta infection, ex vivo in RNA copies/mL

Secondary Outcome Measures

Name	Time	Method
Compare the placental infection of TONV versus ZIKV.	inclusion	Analysis of histological lesions depending on the virus (ZIKV vs TONV) in RNA copies/mL
Validate the ex vivo placental model for TONV.	Inclusion	Analysis of viral load in placental explants for TONV in RNA copies/mL
Compare viral infection of the placenta at different terms of pregnancy (first trimester and term).	term	Analysis of the viral load according to the term in RNA copies/mL
Highlight the cellular targets of TONV.	inclusion	Histological analysis and labeling of placental cells in RNA copies/mL