# The Avian Influenza Virus PA Protein Recruits Host RPS27A to Support Viral Replication

## TL;DR

This study identifies how the avian influenza virus uses a host protein, RPS27A, to aid its replication, offering new insights into viral infection mechanisms.

## Contribution

The novel finding is that the viral PA protein interacts with RPS27A to support early replication of avian influenza virus.

## Key findings

- Transcriptomics showed host responses involving translation, metabolism, and immune signaling during AIV infection.
- PA interacts with host proteins involved in RNA metabolism and ribosome biogenesis, including RPS27A.
- RPS27A supports viral replication during early infection when interacting with PA.

## Abstract

Avian influenza, a disease caused by avian influenza virus (AIV), mainly infects birds but can also infect mammals, which poses a serious threat to public health. Therefore, thorough understanding of its pathogenic mechanism and the identification of antiviral targets are essential for the prevention, control, and treatment of AIV. The polymerase acidic protein (PA) is a core component of the viral RNA-dependent RNA polymerase complex and plays a central role in viral transcription through its cap-snatching activity during early infection. We employed a multi-omics approach combining transcriptome analysis with PA interaction proteomics to characterize host responses during AIV infection and explore the PA–host interaction network. Transcriptomics revealed a polarized host response marked by activated translation-related processes, mitochondrial energy metabolism, and innate immune signaling, alongside broad suppression of nuclear transcriptional regulation and cell cycle pathways. Immunoprecipitation–mass spectrometry identified host proteins associated with PA that were enriched in RNA metabolism, ribosome biogenesis, and protein homeostasis. Integrative analysis of transcriptomic and interactome data, along with protein–protein interaction network analysis, prioritized a subset of high-confidence PA-interacting host factors. Among these, ribosomal protein RPS27A was validated to interact with PA and to support viral replication during early infection in this study.