# Influenza A Virus Infection Induces Preferential Increases in Long-Chain Ceramides

## TL;DR

This study shows that influenza A virus infection changes the levels of specific ceramides in human respiratory cells, with long-chain ceramides increasing significantly.

## Contribution

The study identifies specific ceramide species altered by influenza A virus infection, particularly highlighting increases in long-chain ceramides.

## Key findings

- C16- and C24-ceramide make up about 80% of ceramides in human respiratory epithelial cells.
- IAV infection reduces C16-ceramide and increases C24-ceramide levels.
- Infection leads to a preferential increase in multiple long-chain ceramides.

## Abstract

Influenza is a persistent public health concern worldwide. The elucidation of influenza A virus (IAV)–host interactions and the identification of host factors that regulate IAV infection would be beneficial for combating and treating the disease. Ceramides, comprising a host sphingolipid family, have been shown to regulate virus infections. However, the effect of IAV on individual ceramides remains unknown. This study aimed to investigate the changes in ceramide species during the infection of human lung epithelial A549 cells and human primary tracheal epithelial cells with IAV. We established a method utilizing UHPLC-MS analysis to measure individual ceramides (C14- to C26-ceramide). The results indicate that two main ceramide species, C16- and C24-ceramide, constitute approximately 80% of the ceramide population in human respiratory epithelial cells. Following IAV infection, these ceramides were found to undergo a shift in abundance, with a reduction in C16-ceramide and an increase in C24-ceramide, under various infection conditions. Primarily, IAV infection led to an increase in multiple long-chain ceramides. These findings could provide details for understanding how the ceramide system is disrupted during influenza virus infection and to further support the ongoing efforts to understand influenza–host interactions.