# Sulfatide Binds to Influenza B Virus and Enhances Viral Replication

## TL;DR

This study shows that sulfatide helps influenza B virus replicate and suggests targeting sulfatide could lead to new treatments for influenza.

## Contribution

The novel finding is that sulfatide binds to influenza B virus and enhances its replication, similar to its role in influenza A.

## Key findings

- Sulfatide binds to influenza B virus hemagglutinin and enhances viral replication.
- Sulfatide overexpression increases IBV replication, while sulfatase treatment or anti-sulfatide antibody reduces it.
- Inhibiting sulfatide biosynthesis impairs viral ribonucleoprotein nuclear export and replication.

## Abstract

Seasonal influenza epidemics caused by influenza A viruses (IAV) and influenza B viruses (IBV) pose a substantial public health burden. Despite the significant impact of IBV, its restricted host range and the absence of documented pandemics have resulted in limited research attention relative to IAV. Understanding the viral infection mechanisms of both IAV and IBV is crucial for controlling seasonal epidemics. Previously, we demonstrated that 3′-O-sulfated galactosylceramide sulfatide binds to IAV and enhances viral replication, a finding with potential therapeutic implications. However, the role sulfatide plays in other influenza virus infections, including those caused by IBV, remains unknown. Accordingly, in this paper, we investigate the function of sulfatide during IBV infection. We demonstrate that sulfatide binds to IBV hemagglutinin (HA), and that sulfatide overexpression significantly enhances IBV replication, whereas treatment with sulfatase or an anti-sulfatide antibody markedly suppressed IBV replication. Moreover, further tests involving the inhibition of sulfatide biosynthesis resulted in the suppression of viral replication with impaired nuclear export of viral ribonucleoproteins (vRNPs). These findings establish that sulfatide is a critical regulator of IBV replication, which parallels its role in IAV infection, and suggest that targeting sulfatide-virus interactions can lead to broad-spectrum therapeutic strategies against influenza virus.