scholarly journals Single-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza A virus infection

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Frank S. Heldt ◽  
Sascha Y. Kupke ◽  
Sebastian Dorl ◽  
Udo Reichl ◽  
Timo Frensing
Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 71 ◽  
Author(s):  
Sascha Young Kupke ◽  
Lam-Ha Ly ◽  
Stefan Thomas Börno ◽  
Alexander Ruff ◽  
Bernd Timmermann ◽  
...  

Virus replication displays a large cell-to-cell heterogeneity; yet, not all sources of this variability are known. Here, we study the effect of defective interfering (DI) particle (DIP) co-infection on cell-to-cell variability in influenza A virus (IAV) replication. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNA) and are, thus, defective in virus replication. Moreover, they interfere with virus replication. Using single-cell isolation and reverse transcription polymerase chain reaction, we uncovered a large between-cell heterogeneity in the DI vRNA content of infected cells, which was confirmed for DI mRNAs by single-cell RNA sequencing. A high load of intracellular DI vRNAs and DI mRNAs was found in low-productive cells, indicating their contribution to the large cell-to-cell variability in virus release. Furthermore, we show that the magnitude of host cell mRNA expression (some factors may inhibit virus replication), but not the ribosome content, may further affect the strength of single-cell virus replication. Finally, we show that the load of viral mRNAs (facilitating viral protein production) and the DI mRNA content are, independently from one another, connected with single-cell virus production. Together, these insights advance single-cell virology research toward the elucidation of the complex multi-parametric origin of the large cell-to-cell heterogeneity in virus infections.


Cell Reports ◽  
2021 ◽  
Vol 35 (7) ◽  
pp. 109159
Author(s):  
Xiaoyuan Bai ◽  
Wenxian Yang ◽  
Xiaohan Luan ◽  
Huizi Li ◽  
Heqiao Li ◽  
...  

2007 ◽  
Vol 88 (10) ◽  
pp. 2627-2635 ◽  
Author(s):  
Alexey A. Matskevich ◽  
Karin Moelling

In mammals the interferon (IFN) system is a central innate antiviral defence mechanism, while the involvement of RNA interference (RNAi) in antiviral response against RNA viruses is uncertain. Here, we tested whether RNAi is involved in the antiviral response in mammalian cells. To investigate the role of RNAi in influenza A virus-infected cells in the absence of IFN, we used Vero cells that lack IFN-α and IFN-β genes. Our results demonstrate that knockdown of a key RNAi component, Dicer, led to a modest increase of virus production and accelerated apoptosis of influenza A virus-infected cells. These effects were much weaker in the presence of IFN. The results also show that in both Vero cells and the IFN-producing alveolar epithelial A549 cell line influenza A virus targets Dicer at mRNA and protein levels. Thus, RNAi is involved in antiviral response, and Dicer is important for protection against influenza A virus infection.


2012 ◽  
Vol 206 (4) ◽  
pp. 495-503 ◽  
Author(s):  
Jie Zhou ◽  
Kelvin Kai-Wang To ◽  
Hui Dong ◽  
Zhong-Shan Cheng ◽  
Candy Choi-Yi Lau ◽  
...  

Virulence ◽  
2012 ◽  
Vol 3 (7) ◽  
pp. 603-608 ◽  
Author(s):  
Jason Waithman ◽  
Justine D. Mintern

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