Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates

Mariana Marques, Bruno Ramos, Hélio Albuquerque, Marisa Pereira, Diana Roberta Ribeiro, Alexandre Nunes, Jéssica Sarabando, Daniela Brás, Ana Rita Ferreira, Rui Vitorino, Maria João Amorim, Artur M. S. Silva, Ana Raquel Soares, Daniela Ribeiro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells’ proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.

Original languageEnglish
Article number109100
Number of pages24
JournaliScience
Volume27
Issue number3
DOIs
Publication statusPublished - 15 Mar 2024

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