An emerging #PB2-627 #polymorphism increases the #zoonotic #risk of avian #influenza virus by overcoming ANP32 host restriction in mammalian and avian hosts
ABSTRACT Alterations in the PB2-627 domain of avian influenza virus (AIV) can potentially increase the risk of cross-host species infections in humans and mammals . Recently, there has been a rise in human cases of AIV infections without the presence of the known mammalian determinant PB2-E627K . Here, we identified a variant, PB2-627V , which has evolved in poultry and has contributed to the increase in human AIV infections . By screening global PB2 sequences , we discovered a new independent cluster of PB2-627V that emerged in the 2010s , prevalent in avian, mammalian, and human AIV isolates , including those of H9N2, H7N9, H3N8, 2.3.4.4b H5N1 , and other subtypes. We functionally assessed its host adaptation , fitness , and transmissibility across three subtypes of AIVs (H9N2, H7N9, and H3N8) in different host models . PB2-627V combines the viral properties of avian-like PB2-627E and human-like PB2-627K , facilitating AIVs to efficiently infect and replicate in chickens and mi...