Extreme heterogeneity of influenza virus infection in single cells
- PMID: 29451492
- PMCID: PMC5826275
- DOI: 10.7554/eLife.32303
Extreme heterogeneity of influenza virus infection in single cells
Abstract
Viral infection can dramatically alter a cell's transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription - viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.
Keywords: defective particle; evolutionary biology; genomics; human; infectious disease; influenza virus; interferons; microbiology; single-cell RNAseq; stochasiticity; virus.
© 2018, Russell et al.
Conflict of interest statement
AR, CT, JB No competing interests declared
Figures
Comment in
-
mSphere of Influence: Virology in the noise-how cell-to-cell variability impacts viral infection outcomes.mSphere. 2023 Oct 24;8(5):e0043823. doi: 10.1128/msphere.00438-23. Epub 2023 Sep 25. mSphere. 2023. PMID: 37747254 Free PMC article.
Similar articles
-
Cellular co-infection can modulate the efficiency of influenza A virus production and shape the interferon response.PLoS Pathog. 2020 Oct 16;16(10):e1008974. doi: 10.1371/journal.ppat.1008974. eCollection 2020 Oct. PLoS Pathog. 2020. PMID: 33064776 Free PMC article.
-
Cell-to-Cell Variation in Defective Virus Expression and Effects on Host Responses during Influenza Virus Infection.mBio. 2020 Jan 14;11(1):e02880-19. doi: 10.1128/mBio.02880-19. mBio. 2020. PMID: 31937643 Free PMC article.
-
Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication.Viruses. 2020 Jan 7;12(1):71. doi: 10.3390/v12010071. Viruses. 2020. PMID: 31936115 Free PMC article.
-
Transcriptome Analysis of Infected and Bystander Type 2 Alveolar Epithelial Cells during Influenza A Virus Infection Reveals In Vivo Wnt Pathway Downregulation.J Virol. 2018 Oct 12;92(21):e01325-18. doi: 10.1128/JVI.01325-18. Print 2018 Nov 1. J Virol. 2018. PMID: 30111569 Free PMC article.
-
A Nucleolar Protein, Ribosomal RNA Processing 1 Homolog B (RRP1B), Enhances the Recruitment of Cellular mRNA in Influenza Virus Transcription.J Virol. 2015 Nov;89(22):11245-55. doi: 10.1128/JVI.01487-15. Epub 2015 Aug 26. J Virol. 2015. PMID: 26311876 Free PMC article.
Cited by
-
Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level.Nat Commun. 2024 May 27;15(1):4500. doi: 10.1038/s41467-024-48934-6. Nat Commun. 2024. PMID: 38802391 Free PMC article.
-
Single-cell analysis reveals an antiviral network that controls Zika virus infection in human dendritic cells.J Virol. 2024 May 14;98(5):e0019424. doi: 10.1128/jvi.00194-24. Epub 2024 Apr 3. J Virol. 2024. PMID: 38567950
-
Single-cell herpes simplex virus type 1 infection of neurons using drop-based microfluidics reveals heterogeneous replication kinetics.Sci Adv. 2024 Mar;10(9):eadk9185. doi: 10.1126/sciadv.adk9185. Epub 2024 Feb 28. Sci Adv. 2024. PMID: 38416818 Free PMC article.
-
Single-cell RNA-seq revealed heterogeneous responses and functional differentiation of hemocytes against white spot syndrome virus infection in Litopenaeus vannamei.J Virol. 2024 Mar 19;98(3):e0180523. doi: 10.1128/jvi.01805-23. Epub 2024 Feb 7. J Virol. 2024. PMID: 38323810
-
The use of single-cell RNA-seq to study heterogeneity at varying levels of virus-host interactions.PLoS Pathog. 2024 Jan 18;20(1):e1011898. doi: 10.1371/journal.ppat.1011898. eCollection 2024 Jan. PLoS Pathog. 2024. PMID: 38236826 Free PMC article. Review.
References
-
- Alvaredo F. A note on the relationship between top income shares and the Gini coefficient. Economics Letters. 2011;110:274–277. doi: 10.1016/j.econlet.2010.10.008. - DOI
-
- Amatore D, Sgarbanti R, Aquilano K, Baldelli S, Limongi D, Civitelli L, Nencioni L, Garaci E, Ciriolo MR, Palamara AT. Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS. Cellular Microbiology. 2015;17:131–145. doi: 10.1111/cmi.12343. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials