Viruses are sneaky intruders, hijacking the internal machinery of host cells and replicating out of sight. Understanding these dynamics is the first step to developing effective antiviral strategies that could stop infections, but scientists have largely been left in the dark because there are limited tools to study how viruses move in space and time inside live infected cells, according to Joyce Jose, associate professor of biochemistry and molecular biology at Penn State.
Now, a team of researchers from Penn State led by Jose have filmed the genetic material of Zika and chikungunya viruses - two types of RNA viruses that can cause severe disease and even death in humans - moving inside live infected cells in the laboratory. The research team developed a fluorescent molecular tag that's built into the virus's own genetic material, allowing them to watch in high resolution and in real time how the viral RNA genetic material interacts with its host and replicates. They then used the same tool to identify host proteins that are crucial to life cycles of the viruses.
The novelty of the technique, called a dual-action aptamer tag and described in the study published in the journal Nature Communications, is the tag's two-for-one role - tracking the genetic material and the interacting host proteins, according to the research team. In addition, since the tag doesn't affect the virus's life cycle, scientists can now study how viral genetic material engages with its host during its native infectious life cycle. Jose said this approach could be applied to study other RNA viruses like dengue, hepatitis C and rhinovirus.
"Live imaging like what we've accomplished here is a very powerful tool and is something we've been working toward for the last eight to nine years," said Jose, senior author on the study. "Existing tools like electron microscopy capture fixed images but you lose the temporal resolution, the moment-to-moment interactions between virus and host inside the cell. It's the difference between a photograph and a video."
