An emerging PB2-627 polymorphism increases the pandemic potential of avian influenza virus by breaking through ANP32 host restriction in mammalian and avian hosts
An emerging PB2-627 polymorphism increases the pandemic potential of avian influenza virus by breaking through ANP32 host restriction in mammalian and avian hosts
Guo, Y.; Shu, S.; Zhou, Y.; Peng, W.; Jiang, Z.; Li, Y.; Li, T.; Du, F.; Wang, L.; Chen, X.; Dong, J.; Zhao, C.; Wang, M. H.; Sun, Y.; Sun, H.; Lu, L.; Digard, P.; Chang, K.-c.; Yen, H.-L.; Liu, J.; Pu, J.
AbstractAlterations in the PB2-627 domain could substantially increase the risk of an avian influenza virus (AIV) pandemic. Here, we discovered a variant, PB2-627V, which combines the properties of avian-like PB2-627E and human-like PB2-627K. This variant not only maintains viral fitness in chickens but also facilitates the aerosol transmission of AIVs between ferrets. Mechanistically, PB2-627V utilizes both avian and human host protein ANP32A to support viral polymerase function. Therefore, this mutation overcomes the barrier between birds and humans, greatly enhancing the likelihood of AIVs infecting humans. The PB2-627V polymorphism has been found in birds, humans, and mammals worldwide across more than ten AIV subtypes. Given the escalating global spread of AIVs, it is crucial to closely monitor influenza viruses carrying PB2-627V to prevent a pandemic.