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Influenza remains a critical global threat, having an estimated 1 billion cases annually alongside up to 650,000 deaths (1). Influenza virus infection causes severe respiratory damage that can lead to acute lung injury, and in more severe cases, death. Ubiquitination is a post-translational modification that plays a crucial role in regulating protein activity, stability, and localization during viral infection. It is often utilized in the host innate immune response to fight off viral infection by destroying vital parts of the virus needed for survival and viral replication. E3 ubiquitin ligases are essential for the ubiquitin process by catalyzing the attachment of ubiquitin on targeted substrates. The MARCH (Membrane Associated Ring-CH) family of E3 ligases has been shown to regulate immune responses and viral replication in various viral infections, one being influenza virus. Our lab previously discovered that overexpression of MARCH10 in lung epithelial cells decreased influenza hemagglutinin (HA) when the cells were infected with influenza virus. Based on these findings, we hypothesized that MARCH10 directly targets influenza HA protein for degradation. To investigate the role of MARCH10 on influenza HA, we transiently co-transfected HEK293T cells with control or MARCH10 plasmid in varying doses with influenza HA. Our results indicated that influenza HA protein decreased with increasing amounts of MARCH10. Similarly, when HEK293T ectopically expressed MARCH10 and infected with PR8, influenza HA was found to have a decreased half-life when treated with the protein synthesis inhibitor, puromycin. Furthermore, when V5-tagged MARCH10, FLAG-tagged influenza HA, and HA-tagged ubiquitin were ectopically expressed in HEK293T cells and infected with PR8, MARCH10 was observed to polyubiquitinate influenza HA using a FLAG pulldown immunoassay blot. These findings suggest that influenza HA protein is specifically targeted by the E3 ligase MARCH10 for degradation, which may be useful for developing new therapeutic drugs against influenza virus in the future.