tetano
Editor, Senior Moderator
Npj Viruses
. 2025 Oct 2;3(1):72.
doi: 10.1038/s44298-025-00154-5. Impact of naturally occurring hemagglutinin substitutions on antigenicity and fitness of influenza A(H5N1) virus
Li Wang[SUP] #[/SUP][SUP] 1 [/SUP], Masato Hatta[SUP] #[/SUP][SUP] 1 [/SUP], Chenchen Feng[SUP] #[/SUP][SUP] 1 [/SUP], Paul Carney[SUP] 1 [/SUP], Melvyn R Almanzar-Jordan[SUP] 2 [/SUP], Jieru Wang[SUP] 1 [/SUP], Jaber Hossain[SUP] 1 [/SUP], Ginger Atteberry[SUP] 1 [/SUP], Nacyra Assad-Garcia[SUP] 3 [/SUP], Sydney Sheffield[SUP] 1 [/SUP], Juliana DaSilva[SUP] 1 [/SUP], Juan A De La Cruz[SUP] 1 [/SUP], Yasuko Hatta[SUP] 1 [/SUP], Monique C Johnson[SUP] 1 [/SUP], Julia Frederick[SUP] 1 [/SUP], Rebecca Hart[SUP] 3 [/SUP], Kristine A Lacek[SUP] 1 [/SUP], Malania Wilson[SUP] 1 [/SUP], Lisa M Keong[SUP] 1 [/SUP], Xudong Lin[SUP] 1 [/SUP], Ying Huang[SUP] 1 [/SUP], Michael Currier[SUP] 1 [/SUP], Gene Tan[SUP] 4 5 [/SUP], Sanjay Vashee[SUP] 3 [/SUP], Vivien G Dugan[SUP] 1 [/SUP], Benjamin Rambo-Martin[SUP] 1 [/SUP], Han Di[SUP] 1 [/SUP], Marie K Kirby[SUP] 1 [/SUP], C Todd Davis[SUP] 1 [/SUP], James Stevens[SUP] 1 [/SUP], Bin Zhou[SUP] 6 [/SUP]
Affiliations
In 2024, a human infection with clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) virus was identified in the United States in an individual with no known exposure. Genetic analysis revealed two hemagglutinin (HA) substitutions, P136S and A156T, which may alter viral antigenicity. Virus isolation was unsuccessful, preventing timely serologic analysis. To overcome this limitation, we generated recombinant viruses by reverse genetics and characterized the effects of the substitutions on antigenicity, receptor binding, and replicative fitness. The A156T substitution introduced a potential N-linked glycosylation site, resulting in altered antigenicity and reduced replication in primary human nasal epithelial cells and ferrets. Importantly, the A(H5N1) candidate vaccine virus (CVV) IDCDC-RG80A, which possesses HA-T156, remained antigenically effective against viruses with and without these substitutions. These findings highlight the importance of sequencing, reverse-genetics approaches, and antigenically similar CVVs such as IDCDC-RG80A, for pandemic preparedness against evolving clade 2.3.4.4b A(H5N1) viruses.
. 2025 Oct 2;3(1):72.
doi: 10.1038/s44298-025-00154-5. Impact of naturally occurring hemagglutinin substitutions on antigenicity and fitness of influenza A(H5N1) virus
Li Wang[SUP] #[/SUP][SUP] 1 [/SUP], Masato Hatta[SUP] #[/SUP][SUP] 1 [/SUP], Chenchen Feng[SUP] #[/SUP][SUP] 1 [/SUP], Paul Carney[SUP] 1 [/SUP], Melvyn R Almanzar-Jordan[SUP] 2 [/SUP], Jieru Wang[SUP] 1 [/SUP], Jaber Hossain[SUP] 1 [/SUP], Ginger Atteberry[SUP] 1 [/SUP], Nacyra Assad-Garcia[SUP] 3 [/SUP], Sydney Sheffield[SUP] 1 [/SUP], Juliana DaSilva[SUP] 1 [/SUP], Juan A De La Cruz[SUP] 1 [/SUP], Yasuko Hatta[SUP] 1 [/SUP], Monique C Johnson[SUP] 1 [/SUP], Julia Frederick[SUP] 1 [/SUP], Rebecca Hart[SUP] 3 [/SUP], Kristine A Lacek[SUP] 1 [/SUP], Malania Wilson[SUP] 1 [/SUP], Lisa M Keong[SUP] 1 [/SUP], Xudong Lin[SUP] 1 [/SUP], Ying Huang[SUP] 1 [/SUP], Michael Currier[SUP] 1 [/SUP], Gene Tan[SUP] 4 5 [/SUP], Sanjay Vashee[SUP] 3 [/SUP], Vivien G Dugan[SUP] 1 [/SUP], Benjamin Rambo-Martin[SUP] 1 [/SUP], Han Di[SUP] 1 [/SUP], Marie K Kirby[SUP] 1 [/SUP], C Todd Davis[SUP] 1 [/SUP], James Stevens[SUP] 1 [/SUP], Bin Zhou[SUP] 6 [/SUP]
Affiliations
- PMID: 41034380
- PMCID: PMC12489106
- DOI: 10.1038/s44298-025-00154-5
In 2024, a human infection with clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) virus was identified in the United States in an individual with no known exposure. Genetic analysis revealed two hemagglutinin (HA) substitutions, P136S and A156T, which may alter viral antigenicity. Virus isolation was unsuccessful, preventing timely serologic analysis. To overcome this limitation, we generated recombinant viruses by reverse genetics and characterized the effects of the substitutions on antigenicity, receptor binding, and replicative fitness. The A156T substitution introduced a potential N-linked glycosylation site, resulting in altered antigenicity and reduced replication in primary human nasal epithelial cells and ferrets. Importantly, the A(H5N1) candidate vaccine virus (CVV) IDCDC-RG80A, which possesses HA-T156, remained antigenically effective against viruses with and without these substitutions. These findings highlight the importance of sequencing, reverse-genetics approaches, and antigenically similar CVVs such as IDCDC-RG80A, for pandemic preparedness against evolving clade 2.3.4.4b A(H5N1) viruses.