Influenza D virus utilizes both 9-O-acetylated Nacetylneuraminic and 9-O-acetylated N-glycolylneuraminic acids as functional entry receptors

Tirth Uprety, Jieshi Yu, Aitor Nogales, Ahsan Naveed, Hai Yu, Xi Chen, Yunpeng Liu, Andrew S. Bowman, Luis Martinez-Sobrido, Colin R. Parrish, Gregory B. Melikyan, Dan Wang, Feng Li

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated that IDV binds both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Bovines produce both Neu5,9Ac2 and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. 9-O-Acetylation of sialic acids is catalyzed by CASD1 via a covalent acetyl-enzyme intermediate. To characterize the role of Neu5,9Ac2 and Neu5Gc9Ac in IDV infection and determine which form of 9-O-acetylated sialic acids drives IDV entry, we took advantage of a CASD1 knockout (KO) MDCK cell line and carried out feeding experiments using synthetic 9-O-acetyl sialic acids in combination with the single-round and multi-round IDV infection assays. The data from our studies show that (i) CASD1 KO cells are resistant to IDV infection and lack of IDV binding to the cell surface is responsible for the failure of IDV replication; (ii) feeding CASD1 KO cells with Neu5,9Ac2 or Neu5Gc9Ac resulted in a dose-dependent rescue of IDV infectivity; and (iii) diverse IDVs replicated robustly in CASD1 KO cells fed with either Neu5,9Ac2 or Neu5Gc9Ac at a level similar to that in wild-type cells with a functional CASD1. These data demonstrate that IDV can utilize Neu5,9Ac2- or non-human Neu5Gc9Ac-containing glycan receptor for infection.

Original languageEnglish
JournalJournal of Virology
Volume98
Issue number3
DOIs
StatePublished - Mar 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 American Society for Microbiology. All Rights Reserved.

Keywords

  • 9Ac
  • CASD1
  • Neu5
  • Neu5Gc9Ac
  • influenza D
  • receptor

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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