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Carroll Lab Oxford @carroll-lab.bsky.social · Jul 22

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 · Jul 21

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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.

Carroll Lab Oxford @carroll-lab.bsky.social · Jul 21

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Citation:
Meek et al. Ebola virus persistence: implications for human-to-human transmission and new outbreaks. Explor Med. 2025. doi.org/10.37349/eme...

Ebola virus persistence: implications for human-to-human transmission and new outbreaks

Ebola virus (EBOV) infection usually leads to highly lethal EBOV disease (EVD) with associated viraemia. Viraemia is cleared in those that do survive, however, EBOV may remain hidden in the testes a

doi.org

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Carroll Lab Oxford @carroll-lab.bsky.social · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

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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 · Jul 21

📣 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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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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Citation:
Nguyen et al. SARS-CoV-2 infection enhancement by amphotericin B: implications for disease management. J Virol (2025). doi.org/10.1128/jvi....

SARS-CoV-2 infection enhancement by amphotericin B: implications for disease management | Journal of Virology

AmB and nystatin are common treatments for fungal infections but were predicted to strongly interact with SARS-CoV-2 proteins, indicating their potential modulation or inhibition against the virus. Ho...

doi.org

Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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More broadly, this work underscores the importance of validating in silico drug repurposing predictions with rigorous mechanistic and functional assays. Computational hits may have unanticipated off-target effects in the context of viral co-infections.

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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Key conclusions:
- AmB and nystatin enhance SARS-CoV-2 entry and replication in vitro
- Enhancement is mediated by interference with IFITM3 antiviral function
- Caution is warranted when using AmB in patients with active COVID-19
- Alternative antifungals should be considered

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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Clinical implications: AmB is commonly used to treat COVID-associated mucormycosis. This study suggests it may inadvertently worsen SARS-CoV-2 infection in the lungs, particularly with Omicron and other variants relying more on endocytosis.

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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Previous preprints suggesting AmB as antiviral were based on late timepoint measurements or did not distinguish entry from replication. This study systematically addresses timing, dose, and mechanism.

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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AmB concentrations that enhanced SARS-CoV-2 infection in vitro (0.78–3.12 µM) are within the range found in pulmonary tissue during standard liposomal AmB treatment. This raises concerns for its use during active SARS-CoV-2 infection.

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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In Huh7 cells, AmB and IFITM3 knockdown produced redundant effects, indicating AmB bypasses or suppresses IFITM3 antiviral activity. In Calu-3 cells (which use TMPRSS2-dependent entry), the effect was more modest.

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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Importantly, AmB appears to counteract IFITM3-mediated antiviral restriction, particularly in cell types like Vero E6 and Huh7 that rely on endocytosis for viral entry. This mirrors previous findings with influenza A virus.

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Carroll Lab Oxford @carroll-lab.bsky.social · Jun 24

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RNA-seq analysis showed no significant change in host gene expression, suggesting AmB acts at the biophysical level by altering membrane properties to facilitate viral entry.

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