Ostensibly, the concept of inequality may have some origins in the viral world, as scientists from the University of Minnesota (UMN) Medical School have recently discovered that the influenza virus does not replicate equally in all cells. The investigators found that not only is the immune system response tuned to the amount of virus replication, it's also tuned to the viral spread. This deeper and more accurate understanding of the influenza virus and how it spreads could be the building blocks to better protective therapies for patients in the future. Findings from the new study were published recently in PNAS through an article titled “Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo.”

The seasonal flu is caused by different subtypes of Influenza A virus and typically leads to the death of half a million people each year. In order to study their hypothesis properly, the UMN team first had to create a virus that could not spread—it could replicate, but never get into a new cell.

“To define the antiviral response at the earliest stages of infection we used a series of single-cycle reporter viruses,” the authors wrote. “These viral probes demonstrated cells in vivo harbor a range in magnitude of virus replication. Transcriptional profiling of cells supporting different levels of replication revealed tiers of IFN-stimulated gene expression. Uninfected cells and cells with blunted replication expressed a distinct and potentially protective antiviral signature, while cells with high replication expressed a unique reserve set of antiviral genes.”

Once accomplished, the researchers could then artificially look at virus spread, with the goal of studying how new infections changed after immune responses have started. They found that during virus spread, the second round of replication does not seriously infect ciliated cells, which means the body does a really good job protecting those cells. However other cells weren't protected at all, like type-one alveolar cells which are the cells responsible for gas exchange.

“It's really important to know how cells protect themselves from viruses and how this protection can be imparted on different cell types,” notes senior study investigator Ryan Langlois, Ph.D., assistant professor in the department of microbiology and immunology at the University of Minnesota Medical School. “Clearly it’s not equal. Why it isn't equal, what are the mechanisms driving this, and what this means for disease we don't know yet.”

Thanks to this research, however, researchers now have the building blocks with which to investigate those questions.

“These results change how we view the early infection landscape of cells,” Dr. Langlois remarks. “It brings up new questions, such as what are the earliest viral events and antiviral events that are happening in a host.”

“Together these results highlight the complexity of virus-host interactions within the infected lung and suggest that magnitude and round of replication tune the antiviral response,” the authors concluded.








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