Everybody makes mistakes: how defective viral genomes cause less severe outcomes in influenza infected patients

Influenza virus infections are a leading cause of acute illness and death; according to the Centers for Disease Control and Prevention (CDC), influenza causes 710,000 hospitalizations annually in the United States. Thus, influenza places a huge burden on our healthcare system. More basic research is required to figure out how influenza viruses hide from our immune systems and make us sick.

In nature, influenza viruses are constantly changing due to rapid mutation and natural Screen Shot 2017-11-11 at 2.22.18 PMselection. As a result, the global population of influenza viruses is quite diverse. This diversity can influence how quickly the virus can spread between hosts, and the severity of infection. To determine how influenza virus variability affects disease severity, Vasilijevic et. al. compared a fatal influenza virus to one that only caused mild symptoms. Influenza virus replication isn’t always perfect; sometimes the virus is sloppy, and creates incomplete “defective viral genomes” (DVGs). Vasilijevic et. al. discovered that the mild influenza virus produced significantly more DVGs than its fatal counterpart. These DVGs appear to be important for activating innate antiviral responses in human cells, which evolved to rapidly detect and defeat viruses. This study clearly links precise and faithful influenza virus replication to immune evasion and more severe outcomes of infection.

Influenza DVGs have been described before, but this is the first study that demonstrates the inverse correlation between DVG production and disease severity. Newly-developed deep sequencing technologies may spur the development of diagnostics that could allow us to differentiate between mild high-DVG strains and more severe low-DVG strains. Such technology could inform treatment decisions in the clinic. In the ongoing battle between humans and the constantly-evolving influenza virus, we will take any advantage we can get!

Summary written by: Mariel Kleer

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Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients

Jasmina Vasilijevic, Noelia Zamarreño, Juan Carlos Oliveros, Ariel Rodriguez-Frandsen, Guillermo Gómez, Guadalupe Rodriguez, Mercedes Pérez-Ruiz, Sonia Rey, Isabel Barba, Francisco Pozo, Inmaculada Casas, Amelia Nieto, Ana Falcón

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