Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

The non-polio Enteroviruses enterovirus-D68 (EV-D68) and enterovirus-A71 (EV-A71) are highly prevalent and considered pathogens of increasing health concern. While most enterovirus infections are mild...

The non-polio Enteroviruses enterovirus-D68 (EV-D68) and enterovirus-A71 (EV-A71) are highly prevalent and considered pathogens of increasing health concern. While most enterovirus infections are mild...

Nature Reviews Microbiology - As anti-science sentiment intensifies — aggravated by the pandemic, driven in some parts of the world by political actors and amplified by social media —...

The mechanisms by which Enterovirus D-68 (EV-D68) infection leads to acute flaccid myelitis (AFM), a severe neurological condition characterized by sudden muscle weakness and paralysis, remain poorly ...

Dogs are susceptible to the currently circulating highly pathogenic avian influenza (HPAI) H5 and human H1N1pdm2009 (pandemic H1N1) viruses, yet littl…

Liang et al. shows how contemporary H3N2 viruses reverted to bind sialylated di-LacNAc at the molecular level. Using complex symmetrical and asymmetric N-glycans, major epistatic interactions were rev...

Enterovirus D68 (EV-D68) emerged as a pathogen of increasing health concern globally, particularly due to its association with outbreaks of severe respiratory diseases and acute flaccid myelitis (AFM) in children. Knowledge regarding the tissue tropism and pathogenesis of EV-D68 within the respiratory tract and central nervous system remains limited, primarily due to an incomplete understanding of the host factors that facilitate the entry of EV-D68 into host cells. Several cellular receptors involved in EV-D68 infections have been identified, including ICAM-5, sialylated glycoproteins, and heparan sulfate (HS). Here, we investigate the receptor requirement of a panel of EV-D68 strains covering all clades, focusing on HS and sialosides utilizing glycan arrays. We found that all EV-D68 strains binding to HS harbor a cell culture adaptive substitution in the structural protein VP1 at position 271, which changes the amino acid into a positively charged one. Glycan array analyses revealed that EV-D68 strains prefer α2,6-linked sialic acids presented on N-glycans, α2,8-linked sialic acids on gangliosides, or both. Inhibition of glycolipid biosynthesis or multivalent glycolipid mimics confirmed that ganglioside structures serve as entry receptors for certain EV-D68 strains. Lastly, we examined whether EV-D68 strains that bind to HS or glycolipids require different uncoating mechanisms. Bafilomycin A1 minimally affected the cell entry of HS-binding EV-D68 strains B2/039 and B2/947, and the ganglioside preferring B1/2013 and other viruses were strongly inhibited. Together, we identified that EV-D68 strains can use disialoglycolipids as novel receptors and that different EV-D68 strains show a promiscuous sialic acid binding repertoire.

Enterovirus D68 (EV-D68) emerged as a pathogen of increasing health concern globally, particularly due to its association with outbreaks of severe respiratory diseases and acute flaccid myelitis (AFM) in children. Knowledge regarding the tissue tropism and pathogenesis of EV-D68 within the respiratory tract and central nervous system remains limited, primarily due to an incomplete understanding of the host factors that facilitate the entry of EV-D68 into host cells. Several cellular receptors involved in EV-D68 infections have been identified, including ICAM-5, sialylated glycoproteins, and heparan sulfate (HS). Here, we investigate the receptor requirement of a panel of EV-D68 strains covering all clades, focusing on HS and sialosides utilizing glycan arrays. We found that all EV-D68 strains binding to HS harbor a cell culture adaptive substitution in the structural protein VP1 at position 271, which changes the amino acid into a positively charged one. Glycan array analyses revealed that EV-D68 strains prefer α2,6-linked sialic acids presented on N-glycans, α2,8-linked sialic acids on gangliosides, or both. Inhibition of glycolipid biosynthesis or multivalent glycolipid mimics confirmed that ganglioside structures serve as entry receptors for certain EV-D68 strains. Lastly, we examined whether EV-D68 strains that bind to HS or glycolipids require different uncoating mechanisms. Bafilomycin A1 minimally affected the cell entry of HS-binding EV-D68 strains B2/039 and B2/947, and the ganglioside preferring B1/2013 and other viruses were strongly inhibited. Together, we identified that EV-D68 strains can use disialoglycolipids as novel receptors and that different EV-D68 strains show a promiscuous sialic acid binding repertoire.

There are no vaccines or antivirals available against enterovirus D68. Here, the authors report Jun6504 as a 2C inhibitor and show that it provides broad-spectrum antiviral activity against EV-D68, EV...

The discovery that highly pathogenic avian influenza A(H5N1) virus exhibits a strong tropism for the bovine mammary gland1–4 represents a major shift in our understanding of influenza A virus host ran...