Bat influenza viruses possess an unexpected genetic plasticity

An unprecedented genetic plasticity and a putative function of NA

“Influenza viruses have an inherent high mutation rate,” explains Prof. Martin Schwemmle of the Medical Center – University of Freiburg and coordinator of this study. “We therefore first tested the bat flu virus’ genetic stability to assess its natural mutational potential in cell culture”. To their surprise, within a short period of time all isolated viruses acquired specific amino acid mutations in the viral hemagglutinin (HA) and a truncated neuraminidase (NA) surface glycoprotein. The scientists performed further experiments and showed that these amino acids changes in HA enabled an NA independent viral growth. “Using a variety of mutant viruses, we finally demonstrated that in the absence of a mutated HA, functional NA is required for viral spread”. While the role of the mysterious NA protein has been unknown so far, the researchers found some evidence that its function could be to downregulate cellular MHC-II surface levels to subsequently allow efficient release of infectious viruses from infected host cells.

Potentially low risk for humans

Concerning the potential spill-over risk of the bat influenza virus to the human population, Prof. Schwemmle is cautiously optimistic as he says, “Ferrets are the best small animal model to study human pathogenicity and transmission of sialic acid dependent influenza A viruses. Assuming ferrets are also the appropriate model to study bat flu viruses that instead use MHC-II for cell entry, our study does not provide any indications that these viruses can cause or transmit disease to contact animals. Therefore, the results can be interpreted as that there iscurrently a low zoonotic potential. However, due to the genetic plasticity of these viruses any precise prediction is difficult”.

Nevertheless, this work has raised several open questions that remain to be answered: first, is bat influenza virus NA downregulating MHC-II surface expression and, if so, what is the underlying mechanism? Second, is it possible that bat influenza virus HA proteins can gain affinity to novel cell entry receptors due to their flexibility to accommodate amino acid mutations in HA? “We are currently looking into these questions in greater detail,” says Prof. Schwemmle.

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Media Contact
Dr. Martin Schwemmle
[email protected]
http://dx.doi.org/10.1038/s41564-019-0556-9

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