Human parainfluenza virus infection remodels the host cell glycome

Abstract 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 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. In this study we observed that HPIV-3 infection led to significant host-cell glycome changes in both oligomannose and sialylated complex-type N-glycans. Moreover, notable changes were also observed in both core 1 and core 2 type O-glycans, along with distinct glycosphingolipid remodelling in infected cells compared to their mock-infected counterparts. Our study presents the first evidence that hPIV-3 infection alters host-cell glycome, offering new insights into the virus’s impact on host cellular processes. Competing Interest Statement The authors have declared no competing interest. Footnotes Chemical names have been corrected References have been corrected Abbreviations - HPIV - Human parainfluenza virus - HN - haemagglutinin-neuraminidase - H.p.i - Hour’s post-infection - CEP - Cell extracted protein - SP - Secreted protein - HN - N-acetylglucosamine - H - Hexose - dH - Deoxyhexose - Man - Mannose - N - N-acetylneuraminic Acid - G - N-glycolylneuraminic Acid - GSL - Glycosphingolipids - PGC - Porous graphitized carbon - ESI - Electrospray ionization - CID - Collision induced dissociation