Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein

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Error-prone polymerase function of RNA viruses can result in expression of defective RNAs harboring internal deletions of various sizes. Small subgenomic RNAs are strong inducers of the antiviral response by serving as pathogen-associated patterns that are predominantly detected by cellular sensors. Recently, it has been shown that influenza A virus defective RNAs are not only generated upon passages in cell culture, but also in infected humans, indicating that these subgenomic RNAs may also be relevant in infections in vivo. Here, we characterize a novel defective RNA derived from the PB2 segment of a highly pathogenic H5N1 influenza A virus. This RNA encodes a 10 kDa peptide (PB2Δ) which activates type I interferon (IFN) responses through direct interaction with the adapter protein MAVS, a key component of the RIG-I-dependent IFN induction. This is the first time that such a function was described for a defective RNA-encoded protein, a finding that has several important implications with regard to deciphering viral protein functions and options for immunostimulatory approaches. Furthermore, this is an example of how influenza viruses may acquire novel polypeptides with altered functions from its limited genome.

Vyšlo v časopise: Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004924
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004924

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