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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

13/ Model choice balances safety, cost, ethics, and biology. Integrating advanced human-relevant models is a key future direction.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

12/ BSL-2 surrogates reduce barriers: pseudoviruses (entry only), recombinant Cedar virus (replicating, non-pathogenic). Chimeric CedV expressing NiV/HeV F+G matches receptor tropism and enables BSL-2 pathogenesis studies in immunodeficient mice.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

11/ Syrian hamsters: immunocompetent and permissive; disease depends strongly on route and dose; limited reagents constrain depth. NHPs: closest to human disease, including CNS involvement and relapse, but high cost and ethical/logistical barriers.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

10/ Mice: WT resistant due to type I IFN. IFNAR-KO mice develop lethal disease but omit key IFN-virus interactions. Ferrets: rapid systemic and vascular disease; critical for testing m102.4 mAb efficacy and strain comparisons.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

9/ In vivo models remain essential for vaccine/therapeutic efficacy and safety. No single model fully recapitulates human disease.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

8/ Organ-on-a-chip models combine iPSCs with microfluidics to mimic organ architecture, flow, and mechanical stress. OOC systems were widely used for SARS-CoV-2; not yet applied to henipaviruses but promising for high-containment research.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

7/ Key limitations of in vitro models: lack of circulating immune system, though co-culture approaches are increasingly used.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

6/ Organoids: 3D iPSC-derived tissues capture architecture and cell diversity; compatible with histology and transcriptomics. Advantages of organoids: scalable, cost-effective vs animals, fewer ethical constraints, and can model later-stage pathology.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

5/ Trans-well and air-liquid interface models add barrier function and polarity. Enable TEER, immune migration, and epithelial layering. In porcine airway ALI cultures, NiV spreads mainly cell-to-cell, induces IFN/MHC-I, and causes layer-specific cytopathology.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

4/ Arterial ECs show more syncytia, cell death, and viral RNA than venous ECs, despite weak IFN responses at high viral load.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

3/ Limits of monolayers: single-cell type, no immune context, and phenotypic drift with prolonged culture reduce in vivo relevance. iPSC-derived 2D models improve relevance. Endothelial iPSCs reveal strong arterial EC tropism driven by high EFNB2 expression.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

2/ Cell lines: many are permissive due to widespread ephrin receptors. BHK, Vero, HeLa support high replication; useful for entry/IFN studies. Bat cell lines (esp. Pteropus alecto kidney, lung, brain) enable reservoir-host studies, but lack tissue and immune complexity.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

1/ Henipavirus research is constrained by BSL-4 containment and limited patient samples, making in vitro and in vivo models essential.

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Carroll Lab Oxford @carroll-lab.bsky.social · 20/01/2026

📣 Publication alert 📣 A review paper in @ebiomedicine.bsky.social by @jakubhantabal.bsky.social summarises the current knowledge on host-pathogen interactions of henipaviruses and emerging models to study them. Below is summary thread 2 of 2: Models to study henipaviruses 🧵: @psioxford.bsky.social

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

16/ Major gaps remain in defining cell-type-specific transcriptional responses, spatial immune organization, and cytokine signalling in infected tissues.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

15/ Overall, henipavirus pathogenesis reflects efficient IFN antagonism, endothelial/CNS tropism, dysregulated inflammation, and possible immune-cell involvement.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

14/ Adaptive immunity: seroconversion occurs, but delayed antibody responses and B-cell exhaustion have been reported. NiV activates CD4+ and CD8+ T cells, yet transient T-cell suppression and exhausted phenotypes are observed.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

13/ DC infection may enable “trojan horse” trafficking of virus across the blood-brain barrier. In pigs, NiV has also been detected in CD8+ T cells, but similar infection has not yet been confirmed in humans.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

12/ Henipaviruses may interact directly with immune cells due to ephrin expression on leukocytes. NiV can infect human dendritic cells at low levels; infected DCs induce T-cell apoptosis, suggesting immunosuppression.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

11/ Lung pathology includes interstitial pneumonia, vasculitis, thrombosis, syncytia, haemorrhage, and pneumocyte hyperplasia. Reported pulmonary cytokines include IL-6, IL-8, IL-1α, MCP-1, and G-CSF; neutrophil involvement is hypothesised but unproven.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

10/ The exact CNS cytokine landscape is unknown; TNFα, IL-6, IL-8, CCL2/3/5, and CXCL10 are inferred but not spatially resolved.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

9/ Tissue pathology in NiV/HeV is dominated by vasculitis and inflammation in CNS and lung. CNS lesions show necrosis, encephalitis, and mixed immune infiltrates: lymphocytes, macrophages, neutrophils, and reactive glia.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

8/ CedV is less fusogenic than NiV/HeV, forming fewer syncytia in vitro, a phenotype linked to reduced cytopathic effects.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

7/ CedV infection induces IFN-stimulated genes (e.g. MxA), correlating with effective antiviral control. Receptor usage also contributes to CedV attenuation: absence of ephrin-B3 binding may limit CNS spread.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

6/ CedV is non-pathogenic largely because it lacks P-gene RNA editing and therefore does not express V or W proteins. CedV P protein has low homology to NiV/HeV P; key STAT-binding residues are mostly absent, impairing IFN antagonism.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

5/ NiV W protein translocates to the nucleus via karyopherins α3/4 and interferes with IRF3 and TLR-mediated antiviral pathways. These IFN antagonism mechanisms allow robust viral replication despite host antiviral sensing.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

4/ Innate immunity, especially type I interferon (IFN-I), is a key antiviral barrier targeted by henipaviruses. NiV V protein binds STAT1 in the cytoplasm, blocking phosphorylation and downstream IFN signalling.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

3/ Viral entry is mediated by G glycoprotein binding ephrin-B2 and ephrin-B3 receptors. CedV differs, using multiple ephrin-A/B receptors but not ephrin-B3. Ephrin-B2/B3 are highly expressed in endothelium and CNS neurons, consistent with systemic vasculitis and neuroinvasion seen clinically.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

2/ Henipaviruses are (-)ssRNA paramyxoviruses (~18.2-18.5 kb) encoding N, P, M, F, G, L. The P gene is a major virulence determinant. In NiV/HeV, P-gene mRNA editing generates V, W, and C proteins. Transcript ratios stabilize near 1:1:1 (P:V:W), unusually high for paramyxoviruses.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

1/ Host-pathogen interactions in henipaviruses (NiV, HeV) are central to virulence, immune evasion, and tissue tropism, yet remain incompletely defined.

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Carroll Lab Oxford @carroll-lab.bsky.social · 15/01/2026

📣 Publication alert 📣 A review paper in eBioMedicine by @jakubhantabal.bsky.social summarises the current knowledge on host-pathogen interactions of henipaviruses and emerging models to study them. Below is summary thread 1 of 2: Current knowledge 🧵: @psioxford.bsky.social

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Carroll Lab Oxford @carroll-lab.bsky.social · 22/07/2025

Our lab is attending the UK-ICN (uk-icn.co.uk) AGM this week - look out for out talks! Developing nanobodies as pan-SARS-CoV-2 therapeutics by Luke Jones, today (22/7) at 14:00 High prevalence of sarbecovirus in a single bat roost in Gloucestershire, UK by Dung Nguyen - thursday 24/7 at 9:45

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

14/ This work emphasises the need to integrate virology, epidemiology, and survivor-focused policy to confront EBOV persistence. Future filovirus control will depend as much on understanding within-host dynamics as it does on zoonotic surveillance.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

12/ Conclusion: EBOV persistence—particularly in the testes—poses a rare but high-impact threat to global health. Understanding, detecting, and treating this hidden reservoir is essential for future outbreak prevention and survivor care.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

11/ Implications: – Outbreaks can originate from humans, not just zoonoses – Long-term viral reservoirs complicate eradication efforts – Persistent EBOV challenges current outbreak definitions and requires rethinking public health strategy

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

10/ Key future directions: – Develop testicular in vitro models to study EBOV persistence – Expand semen studies using standardised protocols – Conduct remdesivir phase 3 trials – Investigate female and MSM transmission routes – Monitor post-EVD sequelae linked to persistence

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

9/ Male-to-male sexual transmission remains unexplored in the literature, despite evidence from other viruses suggesting elevated risk via anal intercourse. The authors call for confidential, unbiased contact tracing and NHP challenge studies.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

8/ Vaccination of survivors is unlikely to prevent recrudescence due to already high antibody titres. Ring vaccination of contacts remains the more promising strategy and has shown success in outbreak containment.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

7/ Remdesivir shows promise in reducing EBOV RNA in semen, but trials to date are underpowered. A phase 3 trial in future outbreaks is a critical research priority, alongside further evaluation of favipiravir at higher dosing.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

6/ Despite WHO guidelines, adherence to safe sex and breastfeeding advice is limited by stigma and socioeconomic factors. There is a clear need for long-term follow-up, semen testing, and community-based education to mitigate transmission risk.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

5/ Mechanisms of persistence remain unclear. Three main theories are proposed: – Polymerase mutations reducing viral replication – Defective interfering genomes – Lack of immune pressure in IPNs Of these, polymerase mutation is supported by most evidence.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

4/ Recrudescence (reactivation of virus in IPNs) has caused severe disease, especially meningoencephalitis and uveitis, in multiple survivors. These events are rare but clinically severe and capable of igniting new transmission chains.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

3/ Sexual transmission from persistent virus has previously started outbreaks, including a 2021 outbreak traced to a male survivor infected 5 years prior. Genomic data confirmed the virus was not from a new zoonotic spillover but from the 2013–2016 lineage.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

2/ Persistence is best characterised in semen. Longitudinal cohort studies show EBOV RNA can be detected for up to 988 days. Meta-analysis estimates ~7 of 5,000 male survivors may still be shedding at 5 years post-infection (95% CI: 0–43).

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

1/ The 2013–2016 West Africa EBOV epidemic revealed a critical paradigm shift: EBOV can persist in immune privileged niches (IPNs) such as the testes, brain, and eyes for months to years after recovery, with potential for delayed transmission.

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Carroll Lab Oxford @carroll-lab.bsky.social · 21/07/2025

📣 Publication alert 📣 A new review in Exploration of Medicine by Oliver Meek, Kimberly Fornace & Miles Carroll addresses the long-term persistence of Ebola virus (EBOV) in survivors and its implications for transmission and outbreak control. Thread with key findings below 🧵:

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