Palmenberg Summarizes Biochemistry and Evolution of Rhinovirus C in Virology Review

Photo of Ann Palmenberg

The term “rhino” is derived from the Greek word for “nose.” Hence, human rhinoviruses are those responsible for the common cold and some can even pose a serious threat to those with asthma.

In a recent review article on the cover of the Journal of Virology, biochemistry professor Ann Palmenberg summarizes hers and others’ research on the viruses that cause the common cold and specifically can harm those with asthma.

While two rhinovirus species, called A and B, are the leading cause of the common cold, the C species poses a threat to young children, particularly those with asthma. In recent years, Palmenberg’s research has focused on rhinovirus C, and in 2016, along with collaborators, solved the atomic structure of the virus for the first time. Knowing the structure of a virus is commonly the first step to learning how to combat its effects.

Image of the structure of rhinovirus C
The atomic resolution structure of a
strain of rhinovirus C (rhinovirus C15a).
Image courtesy of the research team.

“These are human-specific viruses, and for a virus to infect a cell it has to recognize the right cell type based on proteins cells display on their surfaces,” explains Palmenberg, who is also a member of the Institute for Molecular Virology. “Rhinoviruses A and B use a protein called ICAM-1 to attach to and enter a cell, but Rhinovirus C uses a different protein, called CDHR3. That is what makes all the difference.”

The biochemistry and genetics behind rhinovirus C are complex. Palmenberg and her team have found a mutation in the CDHR3 protein that changes it slightly, causing the protein to be displayed on the surface of cells significantly more often than those with the regular gene. Approximately 5% of modern humans have this mutation and it causes them to be very susceptible to rhinovirus C and severe asthma attacks, especially in children. Those with the normal gene can also be infected but at a much lower rate, says Palmenberg.

“It’s sort of a snowball effect,” she says. “These kids get put in the hospital with severe asthma attacks because they are genetically programmed to replicate the virus, which is the worst possible virus in the most vulnerable kids. We worked out the biochemistry and a group in Denmark worked out the asthma connection and when we put it all together we knew we had something.”

Image of the cover of the Journal of Virology issue with Palmenberg's review
Palmenberg’s review was on the
cover of the April issue of the 

Journal of Virology.

The next question was — why do some humans have this mutation? That led to the researchers combing through genomic databases collected from across the world, as well as analyzing rhinovirus C samples taken from children in hospitals.

While Palmenberg’s research in this area is ongoing, she says it’s their hypothesis that the gene with the mutation is actually present in all non-human primates like chimps and gorillas and that the now “normal” gene only appeared in humans a few thousand years ago at a much lower level than today.

“At some point rhinovirus C changed receptors to CHDR3 and it must have been pretty devastating,” she says. “At that time, everyone had the version of the gene that allowed the protein to be displayed on their cell surfaces and hence get attacked by the virus.”

Over the last few thousand years the percentage of people with the gene version that causes the protein to be displayed decreased, and the percentage of people whose gene form gives them some protection increased. Today about 95% of people have the protective gene.

“My team and I now want to investigate the structure of the virus when it’s bound to the receptor,” Palmenberg adds. “What’s unusual in the virology world is the breadth of knowledge from biochemistry, epidemiology, and historical genetics that make this really interesting and important story.”