THE ZIKA PUZZLE
answers, but the expediency is clear.
“The stakes are pretty high when you’re
talking about being able to cause birth
defects,” Lazear said.
When Zika enters the fetal brain, it can
disrupt the development of neurons, so the
brain fails to develop. In some cases, it can
cause loss of vision or hearing or can result
in improperly developed joints.
“I think we’re only just beginning to
learn about this spectrum of defects that
the virus can cause, and we really don’t yet
understand exactly why those are happening and what tissues are getting affected and
how the virus causes this damage. We don’t
understand what are the stages of gestation
where the virus is more likely to spread
from the mother to the fetus and where it’s
more likely to damage the fetus.
“There are a lot of unknowns, and it’s
difficult because — of course — pregnant
women and families, they want to know:
‘When is my baby vulnerable? When can I
know that we’re safe?’
“And we don’t have good answers.”
The race to solutions
Lazear’s lab abuts that of Aravinda de
Silva, a professor of microbiology and
immunology in the School of Medicine
who studies the Dengue virus. Dengue
accounts for hundreds of millions of
infections worldwide every year. Dengue
also is Zika’s closest cousin; it does not
cause birth defects.
The research into one virus informs
the other. Stefan Metz, a postdoctoral
fellow in microbiology and immunology, is
building on a Dengue vaccine platform in
de Silva’s lab to create a nanoparticle-based
vaccine for Zika. Instead of using a whole,
replicating virus in the vaccine, which in
Dengue has caused serious side effects,
Metz is using just the portion of a protein
from the surface of the Zika virus that
sparks an immune response in people. By
leaving out the rest, he thinks he can make
a vaccine that’s far safer.
One challenge in studying Zika is that
it doesn’t infect mice very well, so UNC
researchers in another lab are cataloging
mice that better mimic the genetic diversity
found in humans. The labs of Ralph Baric,
a professor of epidemiology, microbiology
and immunology in UNC’s Gillings School
of Global Public Health, and Mark Heise, a
professor of genetics in the medical school,
are screening mice, each of which has a
slightly different scrambled genome, to find
the ones most susceptible to Zika.
“Humans are an outbred population,”
Baric said. “We have mixed genes, so some
of us are highly susceptible to a certain
disease, and some highly resistant to one
but then susceptible to another.”
So these researchers are finding lines of
mice — most of them bred at UNC —
that allow Zika to infect the brain or that
let the virus through the placenta, or both.
The more accurately the mouse model
captures the vastly mixed genetics of the
human population, the more efficiently it
can be used to help humans.
Researchers, clockwise from top left: Aravinda de Silva, Stefan Metz, Ralph Baric, Mark Heise