Penn State Team Films Viral RNA Moving Inside Live Infected Cells

Viruses hijack a host cell’s machinery and replicate largely out of view, but understanding that process is key to developing antivirals. Until now, researchers have lacked good tools for tracking how viruses move through space and time inside actively infected cells.

A Penn State team led by Joyce Jose has now filmed the genetic material of Zika and chikungunya—RNA viruses that can cause severe illness and death—moving inside living infected cells. The researchers built a fluorescent molecular tag directly into the viral genome itself, letting them watch in real time how the RNA interacts with its host and replicates, while also using the same tool to flag host proteins the viruses depend on. Described in Nature Communications, the technique’s distinguishing feature is that single tag’s dual role tracking both the genetic material and the host proteins it interacts with, without interfering with the virus’s life cycle. Jose said the approach could extend to other RNA viruses, including dengue, hepatitis C and rhinovirus. 

“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,” Jose said. “It’s the difference between a photograph and a video.” 

Zika (a relative of West Nile, dengue and yellow fever) and chikungunya (related to Eastern equine encephalitis virus) are both mosquito-borne and have driven repeated outbreaks worldwide, yet neither has an effective antiviral treatment—progress that depends on understanding exactly how each virus exploits its host. That’s historically been difficult to study because viral genomes are so compact that inserting a tracking tag tends to disrupt replication. The team got around this by inserting its aptamer tag, called Mango-II, into the protein-coding region of the viral RNA rather than the regulatory region where such tags are normally placed—an approach not tried before.

In infected human cells, the tagged viruses showed strikingly different behavior: Zika’s RNA stayed anchored to the endoplasmic reticulum, while chikungunya’s moved more widely and rapidly along the plasma membrane, confirming patterns previously reported in the literature. The tag also let researchers pull viral RNA and its bound host proteins out of infected cells, identifying more than 200 host proteins tied to Zika and a smaller set for chikungunya, with 132 shared between them. One shared protein, SFPQ, proved critical to both—suppressing it sharply cut viral production in each.

“Despite being very different viruses, we can say that it’s a host protein that’s important for both viruses to replicate,” Jose said.