A new mouse model to study ZIKA virus infection

Zika virus made global headlines when the World Health Organization declared it a public health emergency in February 2016. A disease transmitted by mosquitoes spread across the Pacific area and Americas like wild fire causing abnormalities in fetus and disorders of the nervous system in adults. Sadly, the disease remains poorly understood till date.

Deciphering nitty-gritty of the disease requires experiments in lab animals. But here’s the problem- there are NO animal models. Now, scientists at the Icahn School of Medicine at Mount Sinai, New York in USA have found the first animal model to study Zika virus. It’s a mouse deficient in a functional STAT2 gene hence it is called a stat2 null mouse. These mice are highly susceptible to ZIKA infection and display disease symptoms identical to those of humans. Interestingly, ZIKA virus does not infect normal adult mice. Only the stat2 null mice get infected because they have a compromised immune system. The other organisms that can be used for the same purpose are rhesus macaque (monkeys) and chicken embryos but they are less feasible because specialized animal facilities and training are required to study ZIKA virus infection in monkeys and chicken.

When the stat2null mice were infected with ZIKA virus, they lost weight, moved lesser, had a hunched posture, showed paralysis of their limbs, and died after a week. Virus spread to the brain, spleen, liver, ovaries, and gonads. The scientists published their results ina recent issue of the journal PLoS Pathogens.

Many people first heard of ZIKA only recently, but this virus is known for almost six decades. It was first isolated in 1947 from a rhesus macaque in the Ziika forest in Uganda, Africa. It caused the first large-scale outbreak in the Yap islands (in the Pacific Ocean outside Africa and Asia) in 2007 infecting more than 7000 individuals. By late 2015, it had spread across South and Central America, the Caribbean and the southern parts of the United States. Importantly, during the 2014 outbreak in Brazil, infections during pregnancy were linked to fetal malformations such as spontaneous abortion, stillbirth, an enlarged head with a small brain, miscarriages, now collectively known as congenital Zika virus syndrome.

Scientists took a step further by studying how differently do the two strains of Zika virus- the African and Asian affect stat2 null mice. They found that viruses from African strain were more virulent and caused short episodes of the disease that resulted in death in most cases. Asian viruses on the other hand, had a prolonged period of infection that occasionally caused death.

“We establish stat2 null mice as new model to study ZIKA virus pathogenesis and demonstrate its utility in highlighting differences induced by different strains leading to severity of disease. The stat2 null mice allow Zika virus infection and recapitulate many aspects of human Zika virus infection such as replication in brain and gonads”, says Dr. Shashank Tripathi, Research Assistant Professor at the Icahn School of Medicine at Mount Sinai, New York in USA.

The research team comprised of Shashank Tripathi, Vinod Balasubramaniam, Julia Brown, Ignacio Mena, Alesha Grant, Susana Bardina, Kevin Maringer, Megan Schwarz, Ana Maestre, Marion Sourisseau, Randy Albrecht, Florian Krammer, Matthew Evans, Ana Fernandez-Sesma, Jean Lim, and Adolfo Garcia-Sastre.

 

Dr. Shashank Tripathi (left), Research Assistant Professor, and Professor Adolfo García-Sastre (right), Director, Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai, New York, USA, who found the mouse model to study ZIKA virus infection.

Reference: PLOS Pathogens 13 (3): e1006258.

By Bhavya Khullar