Host-specific functional #evolution of #seal #influenza A virus #NS1 protein following #avian-to-seal #transmission
ABSTRACT Marine mammals, particularly seals, are susceptible to both avian and human influenza A viruses (IAVs), making them potential intermediates for zoonotic virus emergence . In recent decades, repeated transmissions of avian influenza viruses (AIVs) from wild aquatic birds , their natural reservoir, have caused significant mortality in seals . Defining the molecular determinants of viral adaptation in marine mammals , and their implications for replication in human cells , is therefore essential. The non-structural protein 1 (NS1) of AIV, a key antagonist of the interferon (IFN) response , plays a central role in host adaptation . Here, we analyzed NS1 proteins from seal influenza viruses ( H3, H4, H5, H7 , and H10 subtypes) and their closest avian relatives isolated between 1980 and 2023 , and evaluated their function in seal, avian, and human cells . Phylogenetic analysis confirmed multiple bird-to-seal transmission events . Seal-derived NS1 proteins generally contained f...