It’s remained a mystery exactly how virus are able to penetrate the natural defenses of a cell and invade it, where it hijacks the machinery of a cell to its own advantage. New work published in Nature Communications on a class of viruses called polyomaviruses has revealed more about how polyomaviruses get into cells. Because those viruses can cause cancer and complicate organ transplant, this work could have applications for the treatment of those problems.
"Our results suggest polyomavirus hijacks a kind of cellular molecular motor whose normal job is to transport cargoes, and uses it to build a penetration site or portal," explained one author of the new report, Billy Tsai, Ph.D., of the U-M Medical School Department of Cell and Developmental Biology.
The cellular motor in question is called kinesin-1, which move along tracks in the cell, microtubules, shuttling cargo along it. It appears the polyomavirus uses that mechanism for itself.
"From the cell's point of view it's a mild process," added postdoctoral fellow Madhu Sudhan Ravindran, Ph.D, a member of the research team. "Only a few virus particles end up being successful - but once they are, they can reach the nucleus, letting a while gang of thieves loose.”
Scientists have been working to understand polyomavirus for decades, and this new discovery is a big step forward. While it’s too early to know how big an impact it will have, Tsai noted that there are drugs in development that try to stop cancer cells from dividing.
Researchers already knew that polyomavirus was able to get by the cellular defenses, and is swept up into vesicles that internalize parts of the cell membrane. From there, the virus can hitch a ride in compartments called endosomes to the endoplasmic reticulum (ER), cellular organelles that has roles in protein synthesis and processing. It was not known however, how the virus could get away from the ER and reach the nucleus.
In this new report, the scientists found that the virus attaches to a protein in the ER so it can summon kinesin-1, which is then able to deliver the necessary goods to the virus. If enough virus particles are at the right site, the membrane surrounding the ER can be penetrated (shown in the video at the top). The researchers are now working to uncover the details underlying this process.
"Only a few particles end up being successful, with only one to two percent reaching their final destination," Tsai noted. "They have to be able to do that without destroying the normal function of kinesin-1. Now that we understand this, our goal should be finding a way to destroy this specific kind of motor activity without harming the infected cell."
The researchers also want to know how the virus gets into the nucleus, where it takes over the machinery there, replicating copies of viral DNA.
Learn more about the relationship between polyomavirus and cancer from the video.