NEP: The master regulator of influenza A virus

In our continued efforts to understand the biology of Influenza A virus (IAV), we have characterized RNA from both the host and virus using next generation sequencing. These efforts led to the discovery of a small virus-derived RNA (svRNA) that was necessary for mediating the viral switch from transcription to replication.   Upon characterizing the biology of svRNA, we documented the surprising finding that svRNA synthesis was dependent on the expression of NEP, a minor protein of the virus that slowly accumulates in the cell as a result of inefficient splicing. Together, these two discoveries suggested NEP may be the master regulator of IAV infection. In short, we found that the slow accumulation of NEP provided the virus with a “timer” to coordinate svRNA production and the subsequent switch from transcription to replication. Furthermore, we, and others, have found that NEP-mediated svRNA synthesis is dependent on its capacity to induce cRNA. Despite determining this function for NEP, how it coordinates this activity remains entirely unknown.  Elucidating this biology is of significant interest to the lab.