Scientists published a study (“Influenza A virus surface proteins are organized to help penetrate host mucus”) in eLife that offers new insight on how two proteins help influenza A virus particles gain entrance to human cells.
The findings further explain how influenza A is able to penetrate defensive mucus barriers in the airways and cause infection. This could lead to new opportunities for therapeutic interventions that disrupt this activity, according to the researchers. The World Health Organization (WHO) estimates that between three and five million cases of severe illness and between 250,000 and 500,000 deaths occur every year around the world associated with influenza.
Mucosal barriers are the body’s first line of defense against influenza A infection, containing sialic acid decoys that bind the virus. To infect cells without getting stuck in the mucus, influenza A relies on a balance between two proteins on the surface of its viral particles: the receptor-binding protein hemagglutinin (HA) and the cleaving protein neuraminidase (NA).
But until now, little was known about how these proteins are organized on the particles and how this may contribute to a virus’ ability to penetrate host mucus, the scientists said.
“Although genetic aspects of this balance [between two proteins on the surface of influenza A particles] are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole,” the investigators wrote.
“This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of influenza A.”
“We reasoned that the shape of a virus particle, together with the packaging and organization of HA and NA, could influence the balance of attachment and detachment in ways that allow the virus to effectively penetrate mucus barriers,” says first author Michael Vahey, PhD, formerly a postdoctoral scholar at the University of California, Berkeley, and now assistant professor at Washington University in St. Louis.
More work is now needed to understand if the characteristics of influenza A organization are related to its infectivity in individuals and during host-to-host transmission. The research team thinks that this concept may be at work in other viruses and could be a target for disruption by future treatments.