Granular cytoplasmic inclusions in astrocytes and microglial activation in the fetal brain of pigtail macaques in response to maternal viral infection

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Март 11, 2025

Abstract The fetal origins of neuropsychiatric disorders are poorly understood but have been linked to viral or inflammatory injury the developing brain. white matter is particularly susceptible as myelination, axonal growth, and deep tracts become established. We used pigtail macaque ( Macaca nemestrina ) study maternal effects influenza A virus (FLUAV) Zika (ZIKV) infection during pregnancy, in cohorts with different time intervals between inoculation delivery. observed a striking histopathological alteration subset astrocytes which contained granular cytoplasmic inclusions (“inclusion cells”, ICs) within specific region cerebral brains from FLUAV ZIKV cohorts. Immunohistochemical ultrastructural characteristics ICs indicated that they (GFAP+) undergoing autophagocytosis (p62+) activated lysosomes (LAMP1+, LAMP2+) reactive changes neighboring microglia. There was also positive correlation number LAMP1 LAMP2 immunoreactivity brain (LAMP1: rho 0.66; LAMP2: 0.54, p < 0.001 for both). Interestingly, were significantly more prevalent 5-day cohort 21-day intermediate than controls 0.005 = 0.04, respectively), this relationship not apparent shorter (2–3 days) longer (months) course. Virologic immunologic assays appearance these cells infection. model perinatal hypoxic ischemic encephalopathy. These alterations pathologically abnormal may represent transient neuropathologic finding signifies subtle fetus after

Язык: Английский

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Disruption of functional network development in children with prenatal Zika virus exposure revealed by resting-state EEG

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 21, 2025

Abstract Children born to mothers infected by Zika virus (ZIKV) during pregnancy are at increased risk of adverse neurodevelopmental outcomes including microcephaly, epilepsy, and neurocognitive deficits, collectively known as Congenital Virus Syndrome. To study the impact ZIKV on infant brain development, we collected resting-state electroencephalography (EEG) recordings from 28 normocephalic ZIKV-exposed children 16 socio-demographically similar but unexposed 23–27 months age. We assessed group differences in frequency band power synchrony, well relationship between these metrics A significant difference ( p < 0.05, Bonferroni corrected) Inter-Site Phase Coherence was observed: median Pearson correlation coefficients were 0.15 0.07 children. Results showed that functional networks developing rapidly, part strengthening distal high-frequency weakening proximal lower connectivity, presumably reflecting normal synaptic growth, myelination pruning. These maturation patterns attenuated group, suggesting exposure may contribute vulnerabilities can be detected quantified EEG.

Язык: Английский

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Role of non-human primate models in accelerating research and developing countermeasures against Zika virus infection

The Lancet Microbe, Год журнала: 2025, Номер unknown, С. 101030 - 101030

Опубликована: Фев. 1, 2025

Zika virus, a mosquito-transmitted orthoflavivirus, has become pathogen of global health concern ever since the virus caused an epidemic in Brazil 2015 associated with approximately 700 000 laboratory-confirmed cases congenital microcephaly. The subsequent spread 2016 resulted wide spectrum neurological, ophthalmological, and developmental abnormalities across Americas, Africa, Asia. In this context, non-human primate models have essential tools for research to understand pathogenesis brain injury perinatal complications developing testing medical countermeasures such as vaccines, diagnostics, therapeutics. Fetal been observed various species is influenced by factors strain, gestational age at inoculation, inoculation dose route. Miscarriages are also seen common outcomes first trimester infections. This Series paper reviews diverse currently used mitigate public effects future epidemics.

Язык: Английский

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Persistent innate immune dysfunction and ZIKV replication in the gastrointestinal tract during SIV infection in pigtail macaques

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 4, 2025

Mosquito-borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused widespread epidemics in areas with high HIV prevalence, partly due to the expanded geographic range of arthropod vectors. Despite occurrence large flavivirus outbreaks little is known about effects infection people living (PLWH). Here, we use a pigtail macaque model HIV/AIDS investigate impact simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication pathogenesis. During acute SIV infection, peripheral cellular targets innate immune activation increased. In vitro , blood mononuclear cells (PBMC) from infected macaques were less permissive infection. vivo viremia was delayed more persistent gastrointestinal tissues SIV-ZIKV co-infected animals. This persistence associated changes (monocytes, neutrophils) recruitment tissues, reduced anti-ZIKV immunity, sustained expression inflammatory genes. Collectively, these findings uniquely suggest that untreated may promote responses create state contributes prolonged tract. Furthermore, results PLWH other immunocompromised individuals could be at higher risk for potentially extending window transmission. These insights highlight importance strategies deploying vaccines treatments against ZIKV.

Язык: Английский

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Chronic innate immune impairment and ZIKV persistence in the gastrointestinal tract during SIV infection in pigtail macaques

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 24, 2024

Mosquito borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused global epidemics in areas with high HIV prevalence due to the expanded geographic range of arthropod vectors. Despite occurrence large flavivirus outbreaks countries prevalence, there is little knowledge regarding effects infection people living (PLWH). Here, we use a pigtail macaque model HIV/AIDS investigate impact simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication pathogenesis. Early acute SIV induced expansion peripheral cellular targets increased innate immune activation blood mononuclear cells (PBMC) from infected macaques were less permissive

Язык: Английский

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The Zika virus NS5 protein binds HSP90 to suppress EGF-induced Akt signaling and trophoblast cell migration

Virology, Год журнала: 2024, Номер 603, С. 110370 - 110370

Опубликована: Дек. 28, 2024

Язык: Английский

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