scholarly journals Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

2018 ◽  
Author(s):  
Sunam Gurung ◽  
Nicole Reuter ◽  
Alisha Preno ◽  
Jamie Dubaut ◽  
Hugh Nadeau ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Fetal Death ◽  
Fetal Brain ◽  
Zikv Infection ◽  
Vertical Transfer ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome ◽  
Human Primate ◽  
In Pregnancy

ABSTRACTZika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to a Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and macaques. While microcephaly has been achieved in mice via direct injection of ZIKV into the fetal brain or via interference with interferon signaling, in macaques the primary fetal CZS outcome are ocular defects. In the present study we develope the olive baboon (Papio anubis), as a model for the vertical transfer of ZIKV during pregnancy. We infected four mid-gestation, timed-pregnant baboons with the French Polynesian ZIKV isolate (104ffu) and examined the acute phase of vertical transfer by stopping the study of one dam at 7 days post infection (dpi), two at 14 dpi and one at 21 dpi. All dams exhibited mild to moderate rash and conjunctivitis; three of four dams exhibited viremia at 7 dpi. Of the three dams studied to 14 to 21 days, only one still exhibited viremia on day 14. Vertical transfer of ZIKV to the fetus was found in two pregnancies; in one, vertical transfer was associated with fetal death at ∼14 dpi. In the other, vertical transfer was observed at 21 dpi. Both fetuses had ZIKV RNA in the fetal cerebral cortex as well as other tissues. The 21 dpi fetal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, loss and or damage of immature oligodendrocytes and a loss in neuroprogenitor cells (NPCs). In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL-6 expression. The dams studied to 14 dpi (n=2) and 21 dpi (n=1) exhibited a anti-ZIKV IgM response and IgG response (21 dpi) that included transfer of the IgG to the fetal compartment (cord blood). The severity of systemic inflammatory response (cytokines and chemokines) reflected the vertical transfer of ZIKV in the two pregnancies. As such, these events likely represent the early mechanisms that lead to microcephaly and/or other CNS pathologies in a primate infected with ZIKV and are the first to be described in a non-human primate during the acute phase of ZIKV infection with a contemporaneous ZIKV strain. The baboon thus represents a major NHP for advancing as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs such as macaques.AUTHOR SUMMARYZika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain consistent with development of microcephaly, closely resembling infection in pregnant women. Our baboon model differs from macaque non-human primate models where the primary fetal outcome during pregnancy following infection with contemporary strains of Zika virus is ocular pathology. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and macaques to better understand the disease.

scholarly journals MATERNAL ZIKA VIRUS (ZIKV) INFECTION FOLLOWING VAGINAL INOCULATION WITH ZIKV-INFECTED SEMEN IN THE TIMED-PREGNANT OLIVE BABOON

2020 ◽  
Author(s):  
Sunam Gurung ◽  
Hugh Nadeau ◽  
Marta Maxted ◽  
Jamie Peregrine ◽  
Darlene Reuter ◽  
...  
Keyword(s):  
Puerto Rican ◽  
Zika Virus ◽  
Pregnancy Loss ◽  
Sexual Transmission ◽  
Subcutaneous Route ◽  
Zikv Infection ◽  
Vertical Transfer ◽  
Olive Baboon ◽  
Human Primate ◽  
In Pregnancy

ABSTRACTZIKV infection is associated with pregnancy loss, fetal microcephaly and other malformations. While Aedes sp. of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse and non-human primate (NHP) semen. It is critical to establish NHP models of vertical transfer of ZIKV that recapitulate human ZIKV pathogenesis. We hypothesized that vaginal deposition of ZIKV infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Timed pregnant baboons (n=6) were inoculated via vaginal deposition of baboon semen containing 106 ffu ZIKV (n=3, French Polynesian isolate:H/PF/2013, n=3 Puerto Rican isolate:PRVABC59) at mid-gestation (86-95 days gestation [dG]; term 183dG) on day (d) 0 (all dams), and then at 7 day intervals through three weeks. Maternal blood, saliva and cervico-vaginal washes were obtained at select days post-inoculation. Animals were euthanized at 28 days post initial inoculation (dpi; n=5) or 39 dpi (n=1) and maternal/fetal tissues collected. vRNA was quantified by qPCR. Viremia was achieved in 3/3 FP ZIKV infected dams and 2/3 PR ZIKV. ZIKV RNA was detected in cvw (5/6 dams;). ZIKV RNA was detected in lymph nodes, but not ovary, uterus, cervix or vagina in the FP ZIKV dams but was detected in uterus, vagina and lymph nodes. Placenta, amniotic fluid and all fetal tissues were ZIKV RNA negative in the FP infected dams whereas 2/3 PR infected dam placentas were ZIKV RNA positive. We conclude that ZIKV infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of wide spread dissemination to tissues, including placenta compared to the FP strain.IMPORTANCEDue to its established link to pregnancy loss, microcephaly and other major congenital anomalies, Zika virus (ZIKV) remains a worldwide health threat. Although mosquitoes are the primary means of ZIVK transmission, sexual transmission in human populations is well documented and provides a means for widespread dissemination of the virus. Differences in viremia, tissue distribution, immune responses and pregnancy outcome from sexually transmitted ZIKV compared to the subcutaneous route of infection are needed to better clinically manage ZIKV in pregnancy. Through our previous work, we have developed the olive baboon as a non-human primate model of ZIKV infection that is permissible to ZIKV infection via the subcutaneous route of inoculation and transfer of ZIKV to the fetus in pregnancy. The current study evaluated the course of ZIKV infection after vaginal inoculation of ZIKV in pregnant baboons at mid-gestation using baboon semen as the carrier and comparing two isolates of ZIKV, the French Polynesian isolate first associated with microcephaly and the Puerto Rican isolate, associated with an increased risk of microcephaly observed in the Americas.

scholarly journals Zika virus infection from a newborn point of view. TORCH or TORZiCH?

2018 ◽  
Vol 11 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Adriana Tahotná ◽  
Jana Brucknerová ◽  
Ingrid Brucknerová
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Clinical Symptoms ◽  
Global Climate ◽  
Point Of View ◽  
Zikv Infection ◽  
Global Climate Changes ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome ◽  
The Media

Abstract Zika virus (ZIKV) belongs to the group of viruses called arboviruses. Congenital Zika syndrome is a new disease with infectious teratogenic aetiology. The clinical symptoms are divided into morphological and functional. Most severe complication is the foetal brain disruption sequence that includes severe microcephaly, anomalies of the eyes and congenital contractions of joints. The aim of this paper was to review available facts about Zika virus infection from a newborn point of view in a form of the summary of all important information. Zika virus infection is a problem of past, present and future. Epidemics may occur because of global climate changes, also in countries where natural conditions for life of mosquitos are not present. This clearly indicates the need to continue developing of vaccines and specific antiviral drugs. Until this happens, we must adhere individual preventive measures. Zika virus has proven to us how it can affect the health of adults and neonates but also thinking of healthy people. Newborns with microcephaly on the front pages of the media caused in 2015 panic and fear around the world – for this reason education of people is necessary. Due to serious congenital disorders associated with ZIKV infection and global impact of virus we suggest modifying old acronym TORCH for new TORZiCH to accent the position of Zika virus.

scholarly journals 84. Clarifying the Congenital Zika Syndrome Phenotype and Expanding to Congenital Zika Spectrum in the Absence of Laboratory Evidence

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S173-S173
Author(s):  
Laura D Zambrano ◽  
Augustina Delaney ◽  
Charles E Rose ◽  
Suzanne Gilboa ◽  
Van Tong ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Optic Nerve ◽  
Virus Infection ◽  
Zika Virus ◽  
Congenital Anomalies ◽  
Zikv Infection ◽  
Distinct Phenotype ◽  
Laboratory Evidence ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome

Abstract Background Congenital Zika syndrome (CZS) is a term used to describe the pattern of anomalies in infants due to congenital Zika virus (ZIKV) infection. To date, published reports of infants with these anomalies have been primarily small case series of the most severely affected infants and attempts to determine the CZS phenotype have been based on those reports. Lack of a standard definition has led to inconsistencies in the term’s use in the literature and uncertainty about the full spectrum of anomalies, limiting the application for diagnostic and surveillance purposes. Cluster analysis of brain and eye anomalies associated with congenital Zika infection. Clustering occurred independent of laboratory evidence of Zika virus infection, yielding a clinically distinct phenotype associated with congenital infection. Methods We sought to understand which defects co-occur with possible congenital ZIKV infection using data from 415 mother-infant dyads with laboratory evidence of confirmed or presumptive Zika virus infection from the U.S. Zika Pregnancy and Infant Registry, and a comparison group of 4534 mother-infant dyads with no documented or plausible ZIKV infection from the Zika Birth Defects Surveillance System. We use k-means cluster analysis, discriminant analysis, and regression approaches to identify combinations of defects consistent with possible congenital ZIKV infection. Results A clinically distinct phenotype emerged as a single cluster in infants for whom both brain and eye defects were recorded that corresponded to evidence of confirmed or probable ZIKV infection. A combination of six defects (sub-cortical calcifications, chorioretinal atrophy/pigmentary anomalies, arthrogryposis or clubfoot, cerebral atrophy or ventriculomegaly, abnormal cortical gyration, and optic nerve atrophy/pallor/other optic nerve abnormalities) predicted the presence of laboratory evidence (area under the receiver operating characteristics curve: 0.95, 95% confidence interval: 0.90–0.99). Conclusion Further analyses are underway to develop a scoring rubric to weigh evidence of specific congenital anomalies, separately and in combination, that are consistent with laboratory evidence of congenital ZIKV infection. A quantitatively determined spectrum of Zika-associated anomalies, based on the presence of specific combinations of congenital anomalies, will inform a clinical decision tool to improve patient counseling and public health surveillance practices. Disclosures All Authors: No reported disclosures

scholarly journals Asymptomatic Prenatal Zika Virus Infection and Congenital Zika Syndrome

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Enny S Paixao ◽  
Wei-Yee Leong ◽  
Laura C Rodrigues ◽  
Annelies Wilder-Smith
Keyword(s):  
Virus Infection ◽  
Birth Defects ◽  
Prospective Studies ◽  
Zika Virus ◽  
Retrospective Studies ◽  
Recall Bias ◽  
Virus Infections ◽  
Fetal Outcomes ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome

Abstract To investigate to what extent asymptomatic vs symptomatic prenatal Zika virus infections contribute to birth defects, we identified 3 prospective and 8 retrospective studies. The ratio varied greatly in the retrospective studies, most likely due to recruitment and recall bias. The prospective studies revealed a ratio of 1:1 for asymptomatic vs symptomatic maternal Zika infections resulting in adverse fetal outcomes.

scholarly journals Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yuyi Huang ◽  
Yujie Wang ◽  
Shuhui Meng ◽  
Zhuohang Chen ◽  
Haifan Kong ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cell Line ◽  
Zika Virus ◽  
Fetal Brain ◽  
Host Immunity ◽  
Type I ◽  
Type I Ifn ◽  
Zikv Infection

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

scholarly journals Zika virus infection in pregnancy: Establishing a case definition for clinical research on pregnant women with rash in an active transmission setting

2019 ◽  
Vol 13 (10) ◽  
pp. e0007763 ◽  
Author(s):  
Ricardo Arraes de Alencar Ximenes ◽  
Demócrito de Barros Miranda-Filho ◽  
Elizabeth B. Brickley ◽  
Ulisses Ramos Montarroyos ◽  
Celina Maria Turchi Martelli ◽  
...  
Keyword(s):  
Virus Infection ◽  
Clinical Research ◽  
Pregnant Women ◽  
Zika Virus ◽  
Case Definition ◽  
Transmission Setting ◽  
Zika Virus Infection ◽  
In Pregnancy

scholarly journals ISUOG Interim Guidance on ultrasound for Zika virus infection in pregnancy: information for healthcare professionals

2016 ◽  
Vol 47 (4) ◽  
pp. 530-532 ◽  
Author(s):  
A. T. Papageorghiou ◽  
B. Thilaganathan ◽  
C. M. Bilardo ◽  
A. Ngu ◽  
G. Malinger ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Healthcare Professionals ◽  
Zika Virus Infection ◽  
In Pregnancy

scholarly journals Update on Zika virus infection in pregnancy

2016 ◽  
Vol 62 (2) ◽  
pp. 106-107 ◽  
Author(s):  
Ricardo Simões ◽  
Renata Buzzini ◽  
Wanderley Bernardo ◽  
Florentino Cardoso ◽  
Antônio Salomão ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Zika Virus Infection ◽  
In Pregnancy

scholarly journals Pregnancy alters innate immune responses to Zika virus infection in the genital tract

2019 ◽  
Author(s):  
Kelsey E. Lesteberg ◽  
Dana S. Fader ◽  
J. David Beckham
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Zika Virus ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Innate Immune Responses ◽  
Zikv Infection ◽  
Zika Virus Infection ◽  
Pregnant Mice

AbstractRecent outbreaks of Zika virus (ZIKV) have been associated with birth defects, including microcephaly and neurological impairment. However, the mechanisms which confer increased susceptibility to ZIKV during pregnancy remain unclear. We hypothesized that poor outcomes from ZIKV infection during pregnancy are due in part to pregnancy-induced alteration of innate immune cell frequencies and cytokine expression. To examine the impact of pregnancy on innate immune responses, we inoculated pregnant and non-pregnant female C57BL/6 mice with 5×105 FFU of ZIKV intravaginally. Innate immune cell frequencies and cytokine expression were measured by flow cytometry at day 3 post infection. Compared to non-pregnant mice, pregnant mice exhibited higher frequencies of uterine macrophages (CD68+) and tolerogenic dendritic cells (CD11c+ CD103+ and CD11c+ CD11b+). Additionally, ZIKV-infected pregnant mice had lower frequencies of CD45+ IL-12+ and CD11b+ IL-12+ cells in the uterus and spleen. These data show that pregnancy results in an altered innate immune response to ZIKV infection in the genital tract of mice and that pregnancy-associated immune modulation may play an important role in the severity of acute ZIKV infection.ImportancePregnant females longer duration that viremia following infection with Zika virus but the mechanism of this is not established. Innate immune cellular responses are important for controlling virus infection and are important for development and maintenance of pregnancy. Thus, the acute immune response to Zika virus during pregnancy may be altered so that the pregnancy can be maintained. To examine this interaction, we utilized a mouse model of Zika virus infection during pregnancy using intravaginal inoculation. We found that following Zika virus infection, pregnant mice exhibited increased expression of tolerant or non-inflammatory dendritic cells. Additionally, we found that pregnant mice have significantly depressed ability to secrete the cytokine IL-12 from innate immune cells in the uterus and the spleen while maintaining MHCII expression. These findings show that pregnancy-induced changes in the innate immune cells are biased towards tolerance and can result in decreased antigen-dependent stimulation of immune responses.

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