Dengue: Humanised mouse model paves the way for scientists to understand the complex dengue disease and validate novel therapeutics

- SMART researchers have developed a humanised mouse model for dengue infection that captures key features of the disease, paving the way for scientists to understand the mystery behind the dengue disease and test novel and potential therapeutics for it, before clinical trials.

1.   Singapore    Researchers at the Singapore-MIT Alliance for Research and Technology (SMART)[新加坡-麻省理工学院科研中心]
have developed a
humanised mouse model that will expedite the search for an efficient therapeutic for dengue infection
in the future. This humanised mouse model for dengue is able to capture some of the key features of dengue infection,
such as platelet drop (important symptom and indicator of dengue infection in patients), transient decrease in immune
cell populations in blood and elevation of liver enzymes (common during viral infections in patients). 

2.    Dengue generally affects only humans and specifically uses immune cells for replication. The efforts of finding
the right therapeutics has been undermined due to the absence of animal models to validate the human response to
the dengue infection and study the disease in a human cell context. Now researchers can use the mouse with human
blood cells (humanised mouse) to understand the disease and also validate their dengue therapeutics (vaccine and
treatment) before clinical trials.   

3.   With this new development by the SMART researchers from the Infectious Diseases Interdisciplinary Research Group
(ID IRG), researchers all over the world can now use this humanised mouse model for dengue to test or validate
therapeutics, as well as to understand the disease better in the human cell context (i.e. as close as possible to
that of the disease in the human body).   

4.   Jianzhu Chen 陈建柱, the Ivan R. Cottrell Professor of Immunology at MIT, and SMART Lead Investigator of ID IRG,
said: “The humanised mice have human immune cells as opposed to non-humanised mouse with no human immune
cells at all. Because dengue virus infects only human cells, development of humanised mouse enables us to establish
a small animal model of dengue virus infection. This means that researchers can now test a drug on this mouse and
evaluate the drug’s efficacy more effectively.
   

5.   This research is based on the paper “Inhibition of Megakaryocyte Development in the Bone Marrow Underlies Dengue
Virus-Induced Thrombocytopenia in Humanised Mice”.  Here, the humanised mouse model for dengue was used to
understand an important aspect of the dengue disease – thrombocytopenia or platelet drop and the reason why it
occurs during dengue infection. The abstract can be found at
http://jvi.asm.org/content/early/2013/08/16/JVI.01156-13.abstract
.  The research was funded by the Singapore
National Research Foundation (NRF) through SMART at the Campus for Research Excellence And Technological
Enterprise (CREATE).