NDV at the Human-Animal Interface: Zoonotic Potential and Surveillance Innovation

Newcastle disease virus (NDV), or avian orthoavulavirus 1, is best known as a poultry pathogen, but its biology increasingly plays out at the boundary between birds, people, and the wider environment. The genuine but limited zoonotic risk NDV poses, the One Health framework needed to watch it, the surprising research value of the virus as a vaccine vector and oncolytic agent, and the biosurveillance innovations — from wild-bird sampling to multiplex field tests — that are reshaping how we track it are the subjects of this review.

Rare but Real: NDV in People

The zoonotic potential of NDV is real but narrow. Documented human infections are overwhelmingly mild and self-limiting, presenting as conjunctivitis, sometimes with orbital pain, after direct exposure of the eye to infectious material. Laboratory workers grinding infected tissue, vaccination crews, and poultry handlers not wearing eye protection account for the great majority of cases. Research has described that acute keratoconjunctivitis in a patient whose conjunctival sample yielded NDV reads by metagenomic sequencing, a reminder that zoonotic spillover, occasionally mixed with other ocular pathogens, is still occurring and may be under-reported.

Systemic human illness is uncommon. Mild fever, headache, and malaise have occasionally been described, generally after aerosol exposure, and person-to-person transmission has not been established. Handling or consuming cooked poultry products is not considered a risk. The public-health message is therefore reassuring yet vigilant: the virus is a recognised occupational hazard for people working closely with sick birds, but it does not behave like a pandemic influenza virus in humans.

NDV as a Vaccine Vector and Oncolytic Platform

One of the most active research frontiers treats NDV not as a foe but as a chassis. Using reverse genetics, researchers can insert foreign genes into the NDV genome so that the resulting recombinant virus expresses a heterologous antigen. Because NDV naturally targets and replicates in the cytoplasm, and because certain strains preferentially infect and lyse tumour cells while sparing normal tissue, the virus has been explored both as a vaccine vector against infectious diseases and as an oncolytic agent against cancer.

The oncolytic concept rests on several observed properties. NDV infection can directly kill tumour cells, activate autophagy and apoptosis pathways, and, crucially, stimulate anti-tumour immunity that turns the infected tumour into an in-situ vaccine. Reviews summarise preclinical and early clinical evidence across glioblastoma and other malignancies, noting that recombinant NDV constructs can be engineered to carry therapeutic transgenes and to enhance immune recognition. It is important to stress that these are research concepts under investigation; the value for a diagnostics audience lies in the downstream reagent demand they generate, recombinant NDV fusion and HN proteins, characterised antibodies, and neutralisation standards that also serve veterinary surveillance.

Figure 2. Tumor cell death and the antitumor immune response induced by NDV. (Yang H, et al. 2024)

From a resource perspective, the same glycoprotein antigens that define NDV serology in poultry are the antigens of interest when the virus is repurposed as a vector. A research-grade anti-NDV antibody that blocks fusion or neuraminidase function in a plaque assay today may equally support vector characterization tomorrow. The zoonotic and therapeutic literatures therefore converge on a common need: well-defined, reproducible reagents.

Wild Birds as Long-Distance Dispersers

The global spread of NDV is inseparable from avian migration. Waterfowl and shorebirds carry lentogenic strains along flyways, and periodic spillover into poultry introduces virulent genotypes that can then establish in new regions. Research has documented that the re-emergence of a historically extinct genotype IV NDV in wild and domestic birds across China between 2021 and 2023, with isolates showing striking genetic stability over decades and concerning mismatch against classical vaccine strains. The finding underscores how migratory corridors are not just routes of movement but reservoirs of evolutionary surprise.

Arctic and sub-Arctic surveys add further texture. Detection of a novel gull-associated clade of NDV in Russia's Taimyr Peninsula and the continued isolation of avulaviruses from mallards around Moscow show that even remote breeding grounds circulate paramyxoviruses that may adapt to new hosts. Environmental water sampling, pioneered in Japan's Izumi plain, offers a low-cost way to monitor wild-bird populations without handling individual birds.

African surveillance reinforces the pattern. A review of NDV genotype distribution across the continent highlights how diagnosis, vaccination, and regional collaboration must co-evolve to keep pace with viral diversification. For resource developers, the lesson is that reagents and assays must be validated against the genotypes actually moving along each flyway, not only against historical vaccine strains.

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