Biology subjects

Schoof, N.

Publications and source records attributed to Schoof, N..

3 recordsLinked to original sources

bioRxiv2026

Inhibition of Stemness Pathways during Acute SIV Limits Infection of Central Memory CD4+ T Cells and Alters Viral Reservoir Activity in Macaques

The establishment of a reservoir of latently infected CD4+ T cells that persist on antiretroviral therapy (ART) through proliferation represents the main barrier to HIV cure. Here, we evaluated in macaques a therapeutic approach targeting Wnt and Notch pathways that regulate T cell proliferation and differentiation during acute SIV infection, when the viral reservoir is seeded. The combination of PRI-724 and LY3039478 led to reprogramming of central memory CD4+ T cells away from quiescence and stemness toward a metabolically active effector profile resulting in reduced infection of central memory CD4+ T cells. Following sustained ART, levels of SIV RNA in CD4+ T cells were higher in the PRI-724 + LY3039478-treated group compared to controls, although SIV DNA was similar. These findings suggest that stemness pathway inhibition promotes memory T cell differentiation leading to a more transcriptionally active reservoir and has potential to synergize with "shock-and-kill" approaches to reduce HIV persistence.

microbiology↗

bioRxiv2026

Increased CSF volume, altered brain development and emotional reactivity after postnatal Zika virus infection in infant rhesus macaques

Although congenital Zika virus (ZIKV) syndrome is well-characterized, the neurodevelopmental consequences of postnatal infection are less understood. Here we used a rhesus macaque model to investigate the developmental consequences of ZIKV infection during infancy on the brain and behavior, building on our prior research. Male and female infant rhesus macaques infected with ZIKV at 1 month of age were compared to sex-, age-, and rearing-matched uninfected controls and infants treated with the TLR3 agonist PolyIC as a control for activation of the innate immune system. Longitudinal behavioral assessments revealed alterations in emotional regulation following ZIKV exposure, including poor state control scores obtained from the Infant Neurobehavioral Assessment Scale early after ZIKV infection and longer-term displays of increased hostility during an acute stressor. While attachment bonds to caregivers were preserved, ZIKV-infected infants showed sex-specific alterations in behavioral regulation during caregiver separation compared to controls. At 3 months of age, MRI scans revealed larger total cerebrospinal fluid (CSF) volume and reduced volumes in visual processing regions in ZIKV-infected infants compared to controls. Postnatal ZIKV exposure also resulted in sex-specific brain structural alterations with males exhibiting amygdala hypertrophy, whereas ZIKV-infected females had volumetric reductions in temporal-limbic and temporal-auditory cortices. These findings demonstrate that postnatal ZIKV infection disrupts the development of sensory, social and emotion-regulatory systems and CSF function, highlighting the critical need for long-term monitoring of exposed children. One-Sentence SummaryPostnatal Zika virus infection disrupts emotional regulation and alters brain development in infant rhesus macaques, revealing a critical window of neurodevelopmental vulnerability that extends beyond the fetal period.

neuroscience↗

bioRxiv2026

Mechanisms of disrupted neurodevelopment after Zika virus infection in infancy

Congenital and early-life Zika virus (ZIKV) infection can result in neurologic deficits. Precise mechanisms of injury, especially in the more subtle presentation of postnatal infection, are not fully elucidated. Here, we defined the effects of ZIKV on the developing brain using single cell transcriptomics, histopathology and design-based stereology, diffusion MRI, and neurobehavioral assessments in infant rhesus macaques. ZIKV upregulated interferon-stimulated genes in activated microglia and cell death pathways in neurons and downregulated metabolism and differentiation genes in mature oligodendrocytes. Abnormal micro-organization of the corpus collosum and limbic white matter tracts was seen on diffusion weighted imaging. A curated gene set associated with autism spectrum disorder risk was negatively enriched in inhibitory and excitatory neurons from ZIKV-infected infants, with increased emotional reactivity already evident two weeks following infection. From single cells to organism-level behaviors, these results define the pathways and processes disrupted by early-life ZIKV infection.

neuroscience↗