Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency

Author Summary Influenza A virus carries its segmented genome inside a lipid envelope. Since genome replication occurs inside the nucleus, the main goal of virus infection is to deliver all genome segments through the cytoplasm into the nucleus. After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. Within a complex maturation process, the endosomal lumen acidifies while the vesicles are transported trough the cytosol. If and how these early processes affect virus infection remained mostly speculative. To reach a better understanding and to quantify the physical interplay between membrane fusion, genome diffusion and infection, we developed a mathematical model that comprises all initial steps of virus infection until genome delivery. We calibrated our model using experimental data and challenged its predictions using recombinant viruses to introduce perturbations. Our results provide a theoretical framework to understand the importance of the endosomal virus passage before membrane fusion and genome release. We further unraveled RNA degradation as a previously unknown limiting factor for virus infection. Our work will help to make predictions and evaluate newly occurring virus strains, regarding their infection efficiency in a given host cell, by simply considering their pH sensitivity.See it on Scoop.it, via Viruses and Bioinformatics from Virology.uvic.ca
Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency
Source: Viral Bioinformatics