N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses

Journal Article · Sat Jun 01 00:00:00 EDT 2019 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2019.05.048· OSTI ID:1547165

Broszeit, Frederik; Tzarum, Netanel; Zhu, Xueyong; Nemanichvili, Nikoloz; Eggink, Dirk; Leenders, Tim; Li, Zeshi; Liu, Lin; Wolfert, Margreet A.; Papanikolaou, Andreas; Martínez-Romero, Carles; Gagarinov, Ivan A.; Yu, Wenli; García-Sastre, Adolfo; Wennekes, Tom; Okamatsu, Masatoshi; Verheije, Monique H.; Wilson, Ian A.; Boons, Geert-Jan; de Vries, Robert P.

A species barrier for the influenza A virus is the differential expression of sialic acid, which can either be α2,3-linked for avians or α2,6-linked for human viruses. The influenza A virus hosts also express other species-specific sialic acid derivatives. One major modification at C-5 is N-glycolyl (NeuGc), instead of N-acetyl (NeuAc). N-glycolyl is mammalian specific and expressed in pigs and horses, but not in humans, ferrets, seals, or dogs. Hemagglutinin (HA) adaptation to either N-acetyl or N-glycolyl is analyzed on a sialoside microarray containing both α2,3- and α2,6-linkage modifications on biologically relevant N-glycans. Binding studies reveal that avian, human, and equine HAs bind either N-glycolyl or N-acetyl. Structural data on N-glycolyl binding HA proteins of both H5 and H7 origin describe this specificity. Neuraminidases can cleave N-glycolyl efficiently, and tissue-binding studies reveal strict species specificity. The exclusive manner in which influenza A viruses differentiate between N-glycolyl and N-acetyl is indicative of selection.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); Netherlands Organization for Scientific Research (NWO); European Commission (EC); Royal Dutch Academy of Sciences; National Institutes of Health (NIH); Center for Research on Influenza Pathogenesis (CRIP); Center of Excellence for Influenza Research and Surveillance (CEIRS); National Center for Research Resources; The Scripps Research Institute
• Grant/Contract Number: AC02-06CH11357; P41GM103393; 802780; TOPPUNT 718.015.003; VIDI 723.014.005; R56 AI127371; HHSN272201400008C; P41RR001209
• OSTI ID: 1547165
• Alternate ID(s): OSTI ID: 1623648
• Journal Information: Cell Reports, Journal Name: Cell Reports Vol. 27 Journal Issue: 11; ISSN 2211-1247
• Publisher: Elsevier
• Country of Publication: Netherlands
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Cell Biology