Functional characterization of diverse GH43 enzymes encoded in metagenomes of lignocellulose-active microbial communities

Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of 25 group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were 26 isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite 27 rare, and until recently, geographically restricted to wild shorebirds and waterfowl in 28 Australia. The HAs of H15 viruses contain an insertion in the 150-loop of the receptor29 binding site common to this subgroup and a unique insertion in the 260-loop compared 30 to any other subtype. Here, we show that the H15 HA has a high preference for avian 31 receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it 32 is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than 33 all other HAs due to a tilt and opening of the HA1 subunits of head domain. The 34 extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 35 HAs. Furthermore, the elongated 260-loop increases the HA exposed surface and can 36 contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have 37 been shown to cause enhanced disease in mammalian models, further characterization 38 and immune surveillance of H15 viruses is warranted.