Biology subjects

Kabakov, S.

Publications and source records attributed to Kabakov, S..

3 recordsLinked to original sources

bioRxiv2025

Prenatal Zika Virus Exposure Disrupts Social-Emotional Development and Cortical Visual Function in Infant Macaques

Prenatal exposure to Zika virus (ZIKV) results in a spectrum of outcomes, ranging from severe birth defects and early childhood developmental delays to no apparent deficits. However, the mechanisms underlying these outcomes, particularly in the context of different maternal infection conditions, remain poorly defined. In this study, we employed a translational rhesus macaque model of prenatal ZIKV infection to evaluate longitudinal visual and auditory development from 1 to 12 months of age and characterize neurodevelopmental outcomes at 12 months. Pregnant macaques, either flavivirus-naive or with prior dengue virus (DENV) exposure, were inoculated in the first trimester ([~]30 or 45 gestational days) with an Asian or African lineage of ZIKV or received a saline injection as controls. Maternal plasma viremia duration, viral RNA burden at the maternal-fetal interface, and neutralizing antibody titers did not differ between inoculation cohorts or controls. At 12 months, ZIKV-exposed infants demonstrated altered maternal attachment behaviors and reduced inhibition when approaching sensory stimuli compared to controls. Visual pathway function, assessed by electrophysiology, was significantly impaired at 3 months but normalized by 12 months. Hearing loss was more common among ZIKV-exposed infants, although not statistically significant. Developmental outcomes were associated with prenatal ZIKV exposure itself, independent of viremia duration, neutralizing antibody titer, viral lineage, or maternal DENV immunity, and were not mediated by visual impairment or hearing loss. These findings highlight that any prenatal ZIKV exposure can disrupt early neurobehavioral development and visual function, underscoring the need for prevention strategies focused on maternal infection and early intervention.

microbiology↗

bioRxiv2022

Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV-animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.

microbiology↗

bioRxiv2022

Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage Zika virus

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques inoculated with a low dose of African-lineage ZIKV at gestational day (GD) 45. Here, we inoculate eight pregnant rhesus macaques with a higher dose of African-lineage ZIKV at GD 45 to test the hypothesis that adverse pregnancy outcomes are dose-dependent. Three of eight pregnancies ended prematurely with fetal death. ZIKV was detected in both fetal and placental tissues from all cases of early fetal loss. Further refinements of this challenge system (e.g., varying the dose and timing of infection) could lead to an even more consistent, unambiguous fetal loss phenotype for assessing ZIKV countermeasures in pregnancy. These data demonstrate that high-dose inoculation with African-lineage ZIKV causes pregnancy loss in macaques and also suggest that ZIKV-induced first trimester pregnancy could be strain-specific. Author summaryAlthough pregnant rhesus macaques are susceptible to infection with Zika virus (ZIKV), fetal phenotypes can be subtle and variable. Most macaque studies of ZIKV have involved infection with Asian-lineage viruses because these viruses caused Western Hemisphere outbreaks beginning in 2015. African-lineage ZIKV yields more severe adverse fetal outcomes in small animal models. Here, we provide evidence that pregnant macaques infected late in the first trimester using a high dose of African-lineage ZIKV have frequent ZIKV-associated pregnancy loss. This severe phenotype establishes a new model for evaluating countermeasures and reinforces the idea that African-lineage ZIKV infection may be a frequent cause of pregnancy loss in areas where it is endemic depending on the amount of transmitted virus during infection.

pathology↗