Incomplete influenza A virus genomes occur frequently but are readily complemented during localized viral spread

Nature Communications
Nathan T JacobsAnice C Lowen

Abstract

Segmentation of viral genomes into multiple RNAs creates the potential for replication of incomplete viral genomes (IVGs). Here we use a single-cell approach to quantify influenza A virus IVGs and examine their fitness implications. We find that each segment of influenza A/Panama/2007/99 (H3N2) virus has a 58% probability of being replicated in a cell infected with a single virion. Theoretical methods predict that IVGs carry high costs in a well-mixed system, as 3.6 virions are required for replication of a full genome. Spatial structure is predicted to mitigate these costs, however, and experimental manipulations of spatial structure indicate that local spread facilitates complementation. A virus entirely dependent on co-infection was used to assess relevance of IVGs in vivo. This virus grows robustly in guinea pigs, but is less infectious and does not transmit. Thus, co-infection allows IVGs to contribute to within-host spread, but complete genomes may be critical for transmission.

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Citations

Nov 16, 2019·PLoS Pathogens·Alfred T HardingNicholas S Heaton
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·Katherine E E Johnson, Elodie Ghedin
Sep 30, 2020·Annual Review of Virology·Yannis Michalakis, Stéphane Blanc
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Jun 2, 2021·PLoS Pathogens·Daniel H GoldhillWendy S Barclay
Nov 28, 2021·Nature Communications·Asher LeeksMelanie Ghoul

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Methods Mentioned

BETA
electron microscopy
flow cytometry
PCR
lavage
single-cell assay
FCS
genetic modification
FACS

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