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

Nathan T. Jacobs, Nina O. Onuoha, Alice Antia, John Steel, Rustom Antia and Anice C. Lowen ()
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Nathan T. Jacobs: Emory University School of Medicine
Nina O. Onuoha: Emory University School of Medicine
Alice Antia: Emory University School of Medicine
John Steel: Emory University School of Medicine
Rustom Antia: Emory University
Anice C. Lowen: Emory University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11428-x

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