Dysregulation of M segment gene expression contributes to influenza A virus host restriction

• DOI: 10.1371/journal.ppat.1007892
• Publication Date: 2019-08-15T17:27:43Z
• Authors: Brenda M. Calderon; Shamika Danzy; Gabrielle K. Delima; Nathan T. Jacobs; Ketaki Ganti; Megan R. Hockman; Graeme L. Conn; Anice C. Lowen; John Steel
• Keywords: Viral Shedding

The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate genetic contributions to host adaptation, and underlying mechanisms, we examined a panel isogenic viruses that carry avian- or human-derived segments. Avian, but not human, segments restricted viral growth transmission mammalian model systems, correlated with increased expression M2 relative M1. overexpression was associated intracellular accumulation autophagosomes, which alleviated by interference proton channel activity amantadine treatment. As M1 are expressed from mRNA through alternative splicing, separated synonymous non-synonymous changes differentiate avian found dysregulation gene leading diminished replication, irrespective amino acid composition M2. Moreover, spite efficient possessing protein at low level did transmit efficiently. We conclude (i) determinants reside IAV protein, (ii) control is critical aspect adaptation needed prevent M2-mediated vesicular homeostasis.