A systematic view on influenza induced host shutoff

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Viruses often induce host shutoff to suppress cellular functions and promote viral replication.
• Influenza A virus (IAV) employs strategies to control host cell machinery, but the precise mechanisms of host shutoff remain under investigation.

Purpose of the Study:

• To investigate the molecular mechanisms by which Influenza A virus (IAV) induces host shutoff.
• To determine whether viral transcripts are preferentially translated during IAV infection.
• To identify cellular transcripts that are resistant to IAV-induced shutoff and their functional relevance.

Main Methods:

• RNA-sequencing and ribosome profiling were used to analyze transcript levels and translation efficiency during IAV infection.
• Quantitative analysis of viral and cellular mRNA populations and their translation rates.
• Assessment of the impact of oxidative phosphorylation on viral propagation.

Main Results:

• IAV infection leads to a decline in cellular protein synthesis primarily through viral takeover of the mRNA pool, not preferential translation of viral RNAs.
• Significant variability exists in the reduction of cellular transcripts, with shorter transcripts being less affected.
• Cellular mRNAs involved in oxidative phosphorylation are refractory to IAV-induced shutoff and are crucial for viral propagation.

Conclusions:

• IAV-induced host shutoff is mediated by a viral takeover of the mRNA pool, impacting cellular translation.
• Short cellular transcripts, particularly those involved in essential cell maintenance processes like oxidative phosphorylation, escape IAV-induced shutoff.
• Sustained oxidative phosphorylation activity is essential for efficient IAV replication, suggesting a complex interplay between viral strategy and host cell metabolism.