Orthopoxvirus model review highlights gaps in translational research

A newly published review in Voprosy virusologii examines the state of in vitro and in vivo laboratory models for orthopoxviruses, asking a practical question with growing veterinary relevance: how do researchers study viruses such as mpox, cowpox, and camelpox when no single lab system fully reflects how these infections behave across hosts? The paper arrives as orthopoxviruses remain part of the global zoonotic preparedness conversation, with WHO and WOAH both continuing to stress surveillance, laboratory capacity, and cross-sector coordination. (virusjour.crie.ru)

That timing matters. Since the multicountry mpox emergency beginning in 2022, orthopoxvirus research has expanded well beyond outbreak response into longer-term questions about reservoirs, host range, pathogenesis, and countermeasure development. WHO’s current mpox framework calls for sustained surveillance and preparedness through a One Health lens, while WOAH continues to urge countries to report animal cases and reduce human-to-animal spillback risk. In other words, the research-model question isn’t academic housekeeping. It sits directly underneath how the field validates diagnostics, screens antivirals, and interprets transmission risk across species. (who.int)

The review’s core point is familiar but still unresolved: every model solves one problem and creates another. Prior mpox model reviews show that common in vitro systems include immortalized monkey and human cell lines, along with primary cells and 3D cultures. These are cost-effective and controllable, but they don’t consistently reproduce physiologic conditions or the full disease phenotype. On the in vivo side, mice, rabbits, prairie dogs, squirrels, and non-human primates have all been used, each with different strengths for studying transmission, tissue tropism, immune response, or therapeutic efficacy. Yet even widely used animal models can fail to reproduce key clinical features, while primate models, though often more faithful, come with major ethical and logistical constraints. (pubmed.ncbi.nlm.nih.gov)

Recent literature suggests the field is now pushing hardest on “bridge” models that are more biologically relevant than standard cell culture but less burdensome than primate studies. A 2025 Journal of Virology minireview notes that conventional cell lines support robust mpox infection but miss important disease manifestations, while human organoids can better preserve tissue architecture and function. That same review points to skin, kidney, brain, intestinal, rectal, and liver organoid systems, plus macrophage-augmented organoids and reconstructed human skin platforms, as promising tools for studying tissue tropism, inflammatory responses, and therapeutic testing. At the same time, the authors note these systems still have gaps, especially around immune-cell interactions and full-body disease complexity. (pure.eur.nl)

Industry and public health reaction is less about any single paper than about the broader direction of the field. WHO’s preparedness documents continue to frame mpox control around stronger surveillance, lab capacity, vaccination strategy, and coordination across sectors, while CDC guidance for veterinarians underscores that animal exposure management, clinic flow, and testing criteria remain practical concerns in the real world. WOAH has taken a similarly explicit stance on the need to prevent spillback from infected people to animals, especially mammals that may be susceptible. Together, those signals reinforce the need for better translational models that can inform both bench science and veterinary response protocols. (who.int)

Why it matters: For veterinary professionals, the value of this review is in what it clarifies about evidence quality. When new data appear on orthopoxvirus transmission, vaccine performance, antiviral activity, or host susceptibility, the model behind the claim matters. Findings from immortalized cell lines may be useful for screening but weak for predicting tissue-level disease. Rodent or rabbit data may help with pathogenesis or countermeasure ranking, but not necessarily with species-specific clinical expectations. More advanced organoid and ex vivo systems may improve translational relevance, especially for skin and mucosal disease, but they’re still emerging and not yet a substitute for integrated animal and field data. That’s especially important in veterinary settings where clinicians, diagnosticians, and public health partners may be asked to interpret sparse evidence during a zoonotic event. (pubmed.ncbi.nlm.nih.gov)

The review also reinforces a broader One Health point: orthopoxvirus preparedness depends on connecting human, animal, and laboratory evidence, not treating them as separate tracks. As WHO’s post-emergency mpox strategy shifts toward longer-term control and prevention of both person-to-person and zoonotic transmission, veterinary surveillance and animal-health expertise remain central, not peripheral. Better models should help narrow uncertainty around reservoirs, spillover, spillback, and species susceptibility, but they won’t eliminate the need for coordinated field surveillance and cautious interpretation. (who.int)

What to watch: The next phase is likely to center on validation, not just invention, with researchers comparing organoids, reconstructed tissue systems, and species-specific animal models against real clinical and outbreak data to determine which platforms are most useful for antivirals, vaccines, diagnostics, and transmission studies. (pure.eur.nl)