New human-mimetic tools built by researchers are more likely to succeed in the search for effective treatments for and prevention of flavivirus infections as compared to research using monkeys or other animals as laboratory models. The new study appeared in the journal Frontiers in Cellular and Infection Microbiology. The leader of the study, Dr. David Pamies at the University of Lausanne, along with researchers at John Hopkins University and the National Institute of Allergy and Infectious Diseases' Vaccines Research Center in the United States, includes a comprehensive review of the models used to study deadly mosquito-borne flaviviruses (MBF) such as dengue fever and the Zika virus, known to cause neurological disease in humans.
The authors of the study report that the host specificity of viral diseases presents a challenge for studying these human viruses in animals. Vaccines that proved successful in primate tests have failed in human trials, leading to intense research using knockout and humanized transgenic mice. As a result, human genes relevant to the capacity of the virus to infect humans have been inserted into mice, but these modified animals are still mice, and the researchers appreciate the drawbacks to this approach.
To the researchers, various factors that are recognized to influence the susceptibility of mice to MBF infection that limit applicability to humans. An excellent instance is mice failing to display human disease symptoms if bitten by an infected mosquito, the human route of infection, and the mouse immune response varies depending on the age of the animal. Moreover, the experiments are not reproducible in different laboratories, often an issue in animal experiments.
Along with other colleagues, Dr. Pamies explained, recommending that a future of MBF research with less reliance on primate and rodent models and an increase in in-vitro and in-silicon studies.
Scientists will predict better human pathogenesis and drug efficacy with the emergence of new technologies such as induced pluripotent stem cell models, organotypic cultures, and high throughput in silicon screening. The researchers believe that harmonization to methods and centralization of data, together with combining different approaches to reach a common objective, are crucial to understand MBF infection and neuropathogenesis better and obtain clinical solutions.
As proposed by the investigators, MBF research adopts best non-animal technology practices from other research fields, applying advances such as new brain-specific organoids, multi-cell brain spheroid cultures, blood-brain barrier models and in silicon mathematical modeling for viral replication, disease transmission, and vaccine development.
