Studying the Zika Virus with a New ZIKV Mouse Model
The Zika virus, also known as ZIKV, has become notorious in Brazil, where it had spread during 2015, infecting thousands of people. The main risk of the virus is in its association with the Cuillain-Barre Syndrome, a rare autoimmune disease that can cause microencephaly in newborn infants. While infected adults may only display basic symptoms such as rashes or muscle pain, newborns are highly at risk when exposed to the ZIKV virus. A recent breakthrough by the FDA allowed for a revolutionary immunocompetent ZIKV mouse model to be developed that has helped scientists study the virus more closely than ever before.
New Experimental Animal Models for Studying ZIKV
Many new mouse models susceptible to ZIKV were recently developed in an attempt to study the virus and develop viable treatments or vaccines. Readily available ZIKV mouse models were incapable of showing whether it was the compromised immune system or the virus itself that caused more damage.
To counter this problem, FDA researchers have developed a new ZIKV neonatal model with an immune system that can still respond normally to foreign agents.
It is hoped that the new neonatal mouse pups will help explain and counter neurological disorders like the Cullain-Barre Syndrome more effectively, because their nervous and immune systems are at a similar stage of development as a human mid-term fetus; so relevant and helpful data was expected.
The mice infected with a strain of the Zika virus from Puerto Rico were C57BL/6 strain mice only 1 day old. The animal models were subcutaneously injected with the virus as part of the study, then examined regarding their appearance, ability to move and physical stability. Some of the humanized mouse models were sacrificed to study the impact of ZIKV on the immune system, cells and living tissue more effectively.
Significant Discoveries with the ZIKV Mouse Model
The aforementioned study was reported in PloS Pathogens, and, according to its findings, none of the mice showed any major symptoms – aside from some minor weight gain – for up to 12 days after they were infected with the virus.
Later, symptoms such as hyperactivity, an unsteady stance and loss of mobility were observed in the mice, along with increasingly frequent seizures and loss of balance. After two weeks, most of the mice were able to recover; however, the results have demonstrated that ZIKV induced a slow, non-lethal pathology that displayed strikingly different patterns in mice with healthy vs. non-healthy immune systems.
Examining the ZIKV mouse model, researchers discovered that the virus attaches to white matter in the cerebellum and some areas of the hippocampus – a localization that can explain the effect it had on coordination and movement. ZIKV was also observed to generate a strong inflammatory response in the nervous system that caused immune cells to be sent to fight off the virus. Compared to control mice, neurodegradation in the cerebellum was also discovered.
Since the effect of the virus on this ZIKV mouse model is non-lethal, researchers hope to gain more knowledge studying it long-term. The results have been conclusive in determining that immunocompetent mouse models infected with a strain of the virus can recover from the non-lethal neurological symptoms it induces. The 12-day period before the onset of motor symptoms and the inflammatory response that causes the immune system to react can also be an opportunity to test possible vaccines and treatments on mice.