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Project Summary

Avian influenza viruses (AIV) represent a major zoonotic threat. The antigenic diversity of AIV and the likely absence of pre-existing immunity in the human population means they have pandemic potential. It is thus crucial to identify AIV strains that have high potential for cross-species transmission and to understand their routes for adaptation to humans.

The FLU-SWITCH project addresses the zoonotic potential associated with the switch of H5 and H7 low pathogenic avian influenza viruses (LPAIV) to highly pathogenic avian influenza viruses (HPAIV). Evolution of the typical LPAIV monobasic HA cleavage site (CS) to a multibasic CS is critical to produce an HPAIV. While this step is not the major determinant of AIV adaptation to humans, H5 and H7 strains have caused the majority of zoonotic AIV infections in recent decades and the LPAIV to HPAIV switch is an important facet of this, both for the likelihood of human contact and potential pathogenesis.

FLU-SWITCH will investigate whether specific mutations in the viral genome associated with the LPAIV to HPAIV switch can promote crossspecies transmission and increase the risk of zoonosis. The contribution of host factors to HPAIV emergence will also be investigated to determine how the host species influences LPAIV evolution. As the risk of AIV adaptation to humans is dependent on virus prevalence and geographic distribution, we will analyse the factors modulating HPAIV spread in Europe. Finally, we will analyse the consequences of vaccine-induced pre-existing immunity on the evolution of AIV. We will integrate these parameters to develop a risk assessment tool for the zoonotic potential of AIV.
FLU-SWITCH will generate knowledge on the mechanisms of emergence of AIV with zoonotic potential. Identifying virological markers, host species or environmental factors contributing to their emergence and spread could ultimately be used to eliminate AIV of concerns at source, for the benefit of animal and public health.