Human parainfluenza virus infection remodels the host cell glycome

Human parainfluenza virus type 3 (HPIV-3) remains a major cause of respiratory illness particularly among young children, the elderly and immunocompromised individuals. Despite significant efforts in therapeutic discovery research, there is neither an effective antiviral nor a vaccine available against HPIV-3. Host cell glycosylation is known to play a pivotal role in virus entry and replication. While some host glycan-based cellular receptors for HPIV-3 have been identified, the dynamics of the host-cell glycome upon HPIV-3 infection has never been studied. Herein, we report the first mass spectrometry-based study that provides direct insight into the remodelling of the human lung adenocarcinoma cell (A549) glycome upon HPIV-3 infection. Our results reveal significant remodelling of host-cell glycome, including increased expression of oligomannose and reduced expression of sialylated complex-type N -glycans. In addition, we observed altered O -glycan expression, with upregulation of core 1 and downregulation of core 2 type structures in infected cells compared to mock-infected controls. HPIV-3 infection also led to distinct remodelling of glycosphingolipid glycans. Together, these findings present the first evidence that HPIV-3 infection alters host-cell glycome, offering new insights into the virus’ impact on host-cellular processes.