Scientists pinpoint how the deadly canine parvovirus learned to infect dogs in the 1970s
Canine parvovirus, a highly contagious and deadly virus of dogs, initially infected cats and other animals long before it acquired a few mutations and started a worldwide epidemic in the late 1970s. Now, a team led by the Baker Institute’s Dr. Colin Parrish have worked with Dr. Susan Hafenstein’s laboratory at Penn State University to show exactly how parvovirus enters canine cells, and it’s a surprisingly wobbly interaction.
In a new paper in Proceedings of the National Academy of Sciences, the researchers report that the virus attaches to the pointy end of the transferrin receptor, a protein that all cells use normally to take in iron, and then the virus sways back and forth. It’s possible that this “rock and roll” action causes the virus to change shape and be transported inside the cell, which is the first step on the pathway to infection.
“This shows us structurally how the interaction occurs and specifically how the virus gained the ability to infect dog cells,” said Parrish, the John M. Olin Professor of Virology. “It gets at the fundamental mechanisms of how the canine parvovirus arose in the first place and spread around the world.”
Dr. Heather Callaway, a former graduate student in Parrish’s lab, worked with postdoctoral researcher Dr. Hyunwook Lee in Hafenstein’s group to visualize the interaction using cryo-electron microscopy. This technique allowed them to freeze the purified virus and receptor together, catching them in the act of binding, so that they could see exactly how the attachment occurred.
The new discovery was a long time in the making. Baker researchers, including Drs. Leland Carmichael and Max Appel, first isolated canine parvovirus when it spread worldwide among dogs in 1978, and they quickly developed vaccines that have protected millions of dogs against the disease. In the 1990s, Parrish’s group identified the small genetic changes that enabled the virus to jump from cats and other animals into dogs. And in 1999, his former postdoctoral researcher, now Baker faculty member, Dr. John Parker, identified the transferrin receptor as the Achilles heel that lets parvovirus into the cell, and that specifically controls the infection of dog cells.
“In the future, we are seeking ways to block receptor binding that would prevent virus infection,” said Parrish. Such a drug or antibody could be a lifesaver for infected dogs, especially puppies, which are too young to be vaccinated. In addition, other pathogens use the transferrin receptor to enter cells, including deadly arenaviruses and the malaria parasite, and so treatments that block parvovirus may also stop these other infections.
The research into parvovirus is also part of a broader effort to understand how mutations emerge that let viruses infect new hosts. By figuring out how parvovirus jumped into dogs to cause a pandemic, scientists hope to be able to better predict which viruses are likely to make the leap into humans.
By Patricia Waldron