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Joyce Jose in the laboratory.

Watching viruses at work

Scientist are striving to understand virus biology through live imaging
8 May 2019

Joyce Jose in the laboratory.Joyce Jose grew up in India, where dengue fever is endemic. She saw firsthand the damage that the disease—caused by a virus in the family Flaviviridae, known as flaviviruses, and transmitted by mosquitoes—can do. “In my hometown, my neighbor died of dengue,” said Jose. “It usually appears like flu, but severe dengue can be deadly and people die very quickly.”

Prior to joining the faculty at Penn State as an assistant professor of biochemistry and molecular biology in 2017, Jose studied the structural biology of flaviviruses at Purdue University. In setting up her lab at Penn State, Jose wanted to extend this work to start to see the molecular mechanisms of how these viruses are transmitted, how they interact with receptors on the surface of host cells, and how they target certain organs and cause disease.

Here at Penn State, Jose has the facilities—laboratories with biosafety levels (BSL) 2 and 3, tools for electron microscopy, and live-imaging microscopes—and expert collaborators to do the basic biology that could eventually lead to better ways to combat these viruses.

“The Flaviviridae family includes dengue, West Nile, Zika, and also tick-borne viruses found here in the United States that are much more dangerous,” said Jose. “There are no vaccines for these viruses. There are no antivirals. They are killing people, so a detailed understanding of how they work could lead to the development of better ways to fight these viruses and avoid the toll they take on human lives worldwide.”

Currently, Jose’s lab is mainly working with cell culture, where she can use molecular genetics to “tag” proteins from viruses with fluorescent protein markers that can be seen inside living cells under the microscope. She uses live imaging to track virus proteins to see where in the cell they congregate and how they move from cell to cell. “We know a lot about how viruses manipulate the cells they infect from still images, but with advances in microscopy, we can now watch it as it happens,” said Jose. Her lab also can manipulate the sequence of virus proteins to see how changes to these proteins affect the way the virus interacts with receptors on the surface of host cells. Binding to these receptors allows the virus to enter and infect the cells.

“We do a lot of our research with Zika virus because we have the tools to manipulate its genome and it replicates very quickly in the lab,” said Jose. “Dengue is actually a much bigger public health problem worldwide, but working with dengue virus is very, very difficult because the virus doesn’t grow very fast for live imaging and it is much more difficult to manipulate. But we can use Zika virus to better understand dengue virus and tick-borne flaviviruses.”

One of the next steps for Jose’s research is to start studying the viruses in model organisms. She can already do live imaging in mosquito cells over the course of several days to track how the virus hijacks the host cells to replicate itself.

“Our goal is to increase our understanding of the basic biology of virus function,” said Jose. “This information can hopefully inform the development of effective antivirals and vaccines to fight these viruses.”