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

Details

• Alternative Title:
  Nat Commun
• Personal Author:
  Jacobs, Nathan T. ; Onuoha, Nina O. ; Antia, Alice ; Steel, John ; Antia, Rustom ; Lowen, Anice C.
• Description:
  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.
• Subjects:
  Animals Defective Viruses Disease Models, Animal Dogs Evolution, Molecular Female Genome, Viral Guinea Pigs HEK293 Cells Humans Influenza, Human Influenza A Virus, H3N2 Subtype Likelihood Functions Madin Darby Canine Kidney Cells Models, Biological RNA, Viral Single-Cell Analysis Viral Load Virion Virus Replication Virus Shedding

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• Source:
  Nat Commun. 10
• Pubmed ID:
  31387995
• Pubmed Central ID:
  PMC6684657
• Document Type:
  Journal Article
• Funding:
  R01 AI099000/AI/NIAID NIH HHS/United States ; U19 AI117891/AI/NIAID NIH HHS/United States ; HHSN272201400004C/AI/NIAID NIH HHS/United States
• Volume:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b6b012b32be0db3f5f4270ddf805fc0b70ab0087a4a205e206e1f746a197e5c1
• Download URL:
  https://stacks.cdc.gov/view/cdc/89359/cdc_89359_DS1.pdf
• File Type:
  [PDF - 1.34 MB ]