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.
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.
By
Bhavya Khullar
