Viruses are typically described as tiny, perfectly geometric shells that pack genetic material with mathematical precision, but new research led by scientists at Penn State revealed a deliberate imbalance in their shape that helps them infect their hosts.
The finding, the researchers said, not only illuminates a fundamental viral strategy but also opens doors for antiviral drug design and molecular delivery technologies critical for vaccines, cancer therapies, medication development and gene editing.
The team published their findings today (Dec. 12) in the journal Science Advances and have filed a patent application related to the discovery.
"A virus lacks sensory organs, so it uses chemical cues to determine how it replicates its genetic material into new viral packages or assemblies with precise polarity," said Ganesh Anand, associate professor of chemistry, biochemistry and molecular biology at Penn State and lead author on the study. "This polarity guides the RNA, its genetic material that allows the virus infection to spread, and our research shows that asymmetry is what gives the virus this essential polarity. Viruses build these subtle imperfections into their shells to control how and where their genetic material is packaged and poised to exit during an infection."
The researchers used advanced imaging techniques, conducted at Penn State's publicly funded Core Facilities, to study the architecture of the Turnip Crinkle Virus (TCV). This plant pathogen has an icosahedral - or 20-sided - shell that is the same structure as many human pathogens, such as enteroviruses, noroviruses, poliovirus, hepatitis B virus and the virus that causes chickenpox.
They found that icosahedral viruses use a single chemical bond to tip the scales inside their protein shells to guide release of RNA and infect their hosts. This bond, called an isopeptide link, connects two structural proteins that contribute to the virus's shell and creates a subtle asymmetry that clusters the virus's RNA on one side of the particle, ensuring the genetic material exits in one direction when infecting a host.
