084: How viral-bacterial interactions influence viral infection with Julie Pfeiffer

See the full shownotes at: asm.org/mtm

Julie Pfeiffer tells the story of how she serendipitously found a role for the gut microbiota during polio virus infection, and how she and her lab discovered an important role for bacterial glycans in viral biology. She also talks about viral fitness strategies, and how RNA viruses and DNA viruses benefit from making different amounts of errors when copying their genomes.

Julie's biggest takeaways:

Determining the exact nature of the glycans that play these roles has been difficult because they are very complex. Aspects of lipopolysaccharide, chitin, and peptidoglycan are all sufficient to bind the viral capsid, but because of their structural complexity, it’s difficult to pinpoint the exact molecular interaction.

Bacterial glycan interactions with viruses benefit the virus in two ways: the virus can be delivered to a host cell it will infect, and the viral capsid is stabilized. Whether there is a benefit to the bacterium during these interactions is unknown, but is an active area of research in Julie’s lab.

Many viruses can be inactivated at body temperature or even room temperature if they prematurely release their genetic material. Polio viruses are simply a protein shell surrounding an RNA genome, and the capsid can ‘breathe,’ slightly changing its conformation. Sometimes, the genome is accidentally released, resulting in a viral dead end. Julie showed that bacterial glycans will lock the capsids into a conformation and prevent genome release from happening until the virus encounters a host cell.

Julie is a proponent of clear communication, including with those working in similar fields, which she learned from her experience as a postdoctoral fellow. She and a postdoc in a different institution, Marco Vignuzzi, independently isolated a polio virus mutant that made fewer in genome replication. Both showed that the virus had a defect during mouse infection, indicating that the ability to introduce errors during genome replication is beneficial to viral fitness. Julie and Marco finally met at a viral evolution conference, after which they became close friends.

Featured Quotes (in order of appearance):

“I get more excited about a surprising result because it probably means there’s some interesting underlying biology that couldn’t be anticipated!”

“We’ve done many gross experiments, so buyer beware; you’ve got to know what you’re getting into [with a fecal-oral pathogen].”

“The infectious unit may be more complicated than we think!”

“Communicating with people you know working on similar things can be mutually beneficial for everyone: you both get credit; nobody gets scooped. It’s win-win for sure.”

“The truth is most enteric viral infections are self limiting in most healthy individuals so you’re much better off trudging through a day or two of gastrointestinal illness than blowing up your microbiota.”

Links for this episode

• Julie Pfeiffer website at UT Southwestern Medical Center
• Back-to-back Science publications from Golovkina and Pfeiffer
• PLOS Pathogens: The importance of model systems: Why we study a virus on the brink of global eradication
• Viruses and Cells Gordon conference (donate here)
• HOM Tidbit: Michael Underwood’s A Treatise on the Diseases of Children