Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

  title={Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood},
  author={Stephanie Stanelle-Bertram and Kerstin Walendy-Gnir{\ss} and Thomas Speiseder and Swantje Thiele and Ivy Asantewaa Asante and Carola Dreier and Nancy Mounogou Kouassi and Annette Preuss and Gundula Pilnitz-Stolze and Ursula M{\"u}ller and Stefanie Thanisch and Melanie Richter and Robin Scharrenberg and Vanessa Kraus and Ronja D{\"o}rk and Lynn Schau and Vanessa Herder and Ingo Gerhauser and Vanessa Maria Pfankuche and Christopher K{\"a}ufer and Inken Waltl and Tha{\'i}s Moraes and Julie Sellau and Stefan Hoenow and Jonas Schmidt-Chanasit and Stephanie Jansen and Benjamin Schattling and Harald Ittrich and Udo Bartsch and Thomas Renn{\'e} and Ralf Bartenschlager and Petra Clara Arck and D{\'a}niel Cadar and Manuel A. Friese and Olli Vapalahti and Hanna Lotter and Sany Benites and Lane Rolling and Martin Gabriel and Wolfgang Baumg{\"a}rtner and Fabio Morellini and Sabine M. H{\"o}lter and Oana Veronica Amarie and Helmut Fuchs and Martin Hrabě de Angelis and Wolfgang L{\"o}scher and Froylan Calderon de Anda and G{\"u}lsah Gabriel},
  journal={Nature Microbiology},
Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious… 

Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring

Results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.

Embryonic Stage of Congenital Zika Virus Infection Determines Fetal and Postnatal Outcomes in Mice

The model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice, suggesting that neonatal death in the model could serve as criteria for screening of vaccine candidates.

Animal models of congenital zika syndrome provide mechanistic insight into viral pathogenesis during pregnancy

The animal models developed to study ZIKV-induced adverse outcomes in offspring could provide mechanistic insights into how other viruses, including influenza and hepatitis C viruses, impact placental viability and fetal growth to cause long-term adverse outcome in an effort to identify therapeutic treatments.

Offspring affected with in utero Zika virus infection retain molecular footprints in the bone marrow and blood cells.

It is shown that silent in utero Zika virus infection causes multi-organ inflammation in fetuses and local inflammation in the fetal bone marrow, and In utero infection also caused footprints in the offspring bone marrow and PBMCs.

Reversing neural circuit and behavior deficit in mice exposed to maternal inflammation by Zika virus

It is shown that ZikV infection during mouse pregnancy induces maternal immune activation (MIA) and leads to autistic‐like behaviors including repetitive self‐grooming and impaired social memory in offspring and a hyperconnectivity of vHIP to mPFC projection driving social memory deficits in mice exposed to maternal inflammation by ZIKV is revealed.

The African strain of Zika virus causes more severe in utero infection than Asian strain in a porcine fetal transmission model

This is the first large animal model study which demonstrated that African strain of ZIKV, with no passage history in experimental animals, can cause persistent infection in fetuses and fetal membranes at midgestation.

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice

Different outcomes for the age of infection and sex in wild-type mice are identified: neonatally infected animals presented an increase in PPI and startle latency in both sexes, while adult infected males presented lower startle amplitude but preserved PPI.

Zika virus-induced TNF-α signaling dysregulates expression of neurologic genes associated with psychiatric disorders

It is revealed that cell-intrinsic innate immune responses to ZikV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.

Neurodevelopment in the third year of life in children with antenatal ZIKV-exposure

ABSTRACT We report cognitive, language and motor neurodevelopment, assessed by the Bayley-III test, in 31 non-microcephalic children at age 3 with PCR-confirmed maternal Zika virus exposure (Rio de

Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice.

Evaluated lipid-encapsulated mRNA vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection, finding that the mRNA vaccines elicited higher levels of antigen-specific long-lived plasma cells and memory B cells than the DNA vaccine.



Congenital Zika Virus Infection as a Silent Pathology With Loss of Neurogenic Output in the Fetal Brain

Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly, and suggests that all children exposed to ZikV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Reversing behavioral abnormalities in mice exposed to maternal inflammation

It is shown that cortical abnormalities are preferentially localized to a region encompassing the dysgranular zone of the primary somatosensory cortex (S1DZ), and activation of pyramidal neurons in this cortical region was sufficient to induce MIA-associated behavioural phenotypes in wild-type animals, whereas reduction in neural activity rescued the behavioural abnormalities in MIA-affected offspring.

Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.

A case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week and postmortem analysis of the fetal brain finds substantial brain abnormalities without the presence of microcephaly or intracranial calcifications is described.

Zika Virus Targeting in the Developing Brain

It is found that ZIKV can be transported axonally, thereby enhancing virus spread within the brain and that astrocyte infection may play a more important role in initial infection than previously appreciated.

Bridging Knowledge Gaps to Understand How Zika Virus Exposure and Infection Affect Child Development

The available evidence for neurologic, neurodevelopmental, neurobehavioral, auditory, and vision assessments and management for infants with congenital ZIKV syndrome was critically evaluated.

The Brazilian Zika virus strain causes birth defects in experimental models

It is demonstrated that the ZIKVBR infects fetuses, causing intra-uterine growth restriction (IUGR), and crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, impairing neurodevelopment.