@entity1 @entity281 with avian @entity683 viruses are a serious public health concern. The @entity689 (NA) inhibitors (NAIs) are the frontline anti- @entity683 drugs and are the major option for treatment of newly emerging @entity683 . Therefore, it is essential to identify the molecular markers of @entity11925 resistance among specific NA subtypes of avian @entity683 viruses to help guide clinical management. @entity11925 -resistant substitutions in NA subtypes other than N1 and N2 have been poorly studied. Here, we identified NA @entity3689 substitutions associated with @entity11925 resistance among @entity683 viruses of N3, N7, and N9 subtypes which have been associated with zoonotic transmission. We applied random mutagenesis and generated recombinant @entity683 viruses carrying single or double NA substitution(s) with seven internal genes from A/Puerto Rico/8/1934 (H1N1) virus. In a fluorescence-based NA inhibition assay, we identified three categories of NA substitutions associated with reduced inhibition by NAIs ( @entity684 , @entity685 , and @entity23217 ): (i) novel subtype-specific substitutions in or near the enzyme catalytic site ( @entity69810 , @entity69811 , and @entity69812 , N2 numbering), (ii) subtype-independent substitutions ( @entity52011 /V and/or D and @entity39723 ), and (iii) substitutions previously reported in other subtypes ( @entity29186 , @entity69813 , and @entity69814 ). Our data show that although some markers of resistance are present across NA subtypes, other subtype-specific markers can only be determined empirically. IMPORTANCE: The number of @entity1 infected with avian @entity683 viruses is increasing, raising concerns of the emergence of avian @entity683 viruses resistant to @entity689 (NA) inhibitors (NAIs). Since most studies have focused on @entity11925 -resistance in @entity1 @entity683 viruses, we investigated the molecular changes in NA that could confer @entity11925 resistance in avian viruses grown in immortalized monolayer cells, especially those of the N3, N7, and N9 subtypes, which have caused @entity1 @entity281 . We identified not only numerous @entity11925 -resistant substitutions previously reported in other NA subtypes but also several novel changes conferring reduced susceptibility to NAIs, which are subtype specific. The findings indicate that some resistance markers are common across NA subtypes, but other markers need to be determined empirically for each subtype. The study also implies that antiviral surveillance monitoring could play a critical role in the clinical management of @entity778 and an essential component of pandemic preparedness.

Unique Determinants of XXXX Inhibitor Resistance among N3, N7, and N9 Avian Influenza Viruses.

@entity1 :: ('9606', 'Species') :: ['humans', 'human', 'Human'] @entity11925 :: ('CHEBI:33167', 'Chemical') :: ['NAI'] @entity689 :: ('4758', 'Gene') :: ['neuraminidase'] @entity684 :: ('MESH:D053139', 'Chemical') :: ['oseltamivir'] @entity69810 :: ('p|SUB|R|152|W', 'ProteinMutation') :: ['R152W'] @entity39723 :: ('p|SUB|R|292|K', 'ProteinMutation') :: ['R292K'] @entity685 :: ('MESH:D053243', 'Chemical') :: ['zanamivir'] @entity29186 :: ('p|SUB|Q|136|K', 'ProteinMutation') :: ['Q136K'] @entity69813 :: ('p|SUB|I|222|M', 'ProteinMutation') :: ['I222M'] @entity69814 :: ('p|SUB|E|276|D', 'ProteinMutation') :: ['E276D'] @entity52011 :: ('p|SUB|E|119|G', 'ProteinMutation') :: ['E119G'] @entity778 :: ('MESH:D015658', 'Disease') :: ['influenza virus infection'] @entity69811 :: ('c|SUB|A|246|T', 'DNAMutation') :: ['A246T'] @entity69812 :: ('p|SUB|D|293|N', 'ProteinMutation') :: ['D293N'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infections'] @entity683 :: ('MESH:D007251', 'Disease') :: ['influenza'] @entity23217 :: ('MESH:C414210', 'Chemical') :: ['peramivir'] @entity3689 :: ('D000596', 'Chemical') :: ['amino acid']
@entity689 :: (4758,Gene) :: ['Neuraminidase']
