The bat Influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment
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Abstract
Prior to the discovery of the bat influenza A virus (IAV) subtypes H17N10 and H18N11, it was believed that all IAVs bind via the viral hemagglutinin (HA) to sialic acid residues to mediate attachment and subsequent viral entry. Both HA subtypes, H17 and H18, however, do not bind to sialic acids but instead engage a proteinaceous receptor: major histocompatibility complex class II (MHCII). The mechanistic details of this hitherto unknown protein-mediated entry are not understood. Since conventional IAVs require attachment to clusters of sialylated glycans to overcome the low affinity of the HA-sialic acid interaction, we hypothesized that bat HA would likewise interact with multiple MHCII molecules. Here, we used photoactivated localization microscopy (PALM) on fixed and live cells expressing MHCII fused to appropriate fluorescent reporters. We show that bat IAV particles attach to pre-existing MHCII clusters present on susceptible cells and that the local HA-MHCII interaction results in an increased cluster size. To measure the impact of viral attachment on the dynamics of MHCII, we utilized an experimental setup designated “inverse infection” where intact viral particles were immobilized on coverslips before live MHCII-expressing cells were seeded on top. Recording the trajectories of single MHCII molecules, this approach revealed that the mobility of MHCII was indeed slowed down in viral proximity leading to a local enrichment of MHCII molecules beneath the viral particle. Taken together, these data suggest that attachment of viral particles leads to clustering of MHCII, a process similar to the MHCII dynamics observed during the formation of an immunological synapse.
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Excerpt
Sialic acid, who? Bat influenza A virus H18N11 interacts with host cells by inducing nanoscale MHCII clustering.
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