ETIDIOH - NEW

  Abstract Background :  The H1N1 influenza A virus evades host immunity through continuous antigenic drift, posing a significant challenge to broad-spectrum neutralizing antibody therapies. This study aims to systematically evaluate the neutralizing capacity of the broad-spectrum antibody C12H5 against H1N1 strains from different eras and identify key immune escape mutation sites .  Methods :  Three representative H1N1 virus strains from 2009, 2018, and 2023 were selected. An antigen–antibody binding prediction model based on the ESM-2 large language model was constructed by integrating 48,762 GISAID sequence data and deep mutation scanning data from the Bloom laboratory. Candidate escape sites were screened using SHAP (SHapley Additive exPlanations) value analysis. Mutant viruses were constructed via reverse genetics, and their neutralizing capacity and replication fitness were validated through hemagglutination inhibition assays, microneutralization assays, and vi...

  Abstract We investigated the evolutionary history of the newly emergent neuraminidase (am4N1) associated with the D1.1 and D1.2 genotypes of highly pathogenic avian influenza A(H5N1) viruses in North America . Phylogenetic inference places am4N1 in a sister clade to Eurasian avian, swine, and human A(H1N1)pdm09 viruses and distinct from 1918, pre-2009 human seasonal, and classical swine A(H1N1) lineages . Am4N1 descends from diverse avian N1 genes endemic to the Americas. Phylodynamic analysis indicates a monophyletic am4N1 lineage with numerous introductions of viruses carrying the am4N1 gene likely originating from western Canada into the United States during emergence of the D1.1 and D1.2 genotypes. The lineage has diversified and accumulated deletions in the stalk domain . Despite amino acid divergence, structural modeling shows conserved neuraminidase architecture in the globular head . Given its distinct ancestry and amino acid sequence, further studies are needed to assess...

  Abstract The polymerase acidic (PA) protein is a subunit of the trimeric influenza A virus (IAV) RNA-dependent RNA polymerase and the target of the anti-influenza drug baloxavir marboxil (BXM). As with other direct-acting antivirals , treatment with BXM can lead to selection of viruses carrying resistance mutations . If these mutations have negligible fitness costs, resistant viruses can spread widely and render existing treatments obsolete . Multiple BXM resistance mutations in the nuclease domain of PA have been identified, with I38T and I38M amino acid substitutions occurring frequently. These mutations have minimal to no effects on viral polymerase activity , virus replication , or transmission . However, for reasons that are not well understood, viruses with BXM resistance substitutions have not been able to compete with parental wild-type strains . The IAV genome segment encoding PA also encodes the host shutoff nuclease PA-X, which shares the endonuclease domain with PA bu...

  ABSTRACT The H1N1 influenza virus is a major pandemic and seasonal pathogen with a broad host range , posing a substantial threat to human health and underscoring the need for continuous surveillance . Wild birds , as natural reservoirs of avian influenza viruses (AIVs), carry H1N1 strains capable of reassorting with other influenza viruses, which can drive pandemic emergence. The global migration of wild birds facilitates the spread of these viruses, and their interactions with poultry increase the risk of cross-species transmission , further amplifying the public health threat. However, knowledge of H1N1 genetic diversity in wild birds remains limited. Database analysis shows 80% of avian-origin H1N1 isolates come from wild birds across over 40 countries , mainly in North America, Europe and Asia . This study characterized the molecular traits and genetic evolution of four H1N1 AIVs isolated from common teal and spot-billed ducks during 2019–2021 . Phylogenetic and sequence ana...

  ABSTRACT The outbreak of highly pathogenic avian H5 influenza (HPAI) clade 2.3.4.4b in cattle has spread across the United States . Mice with pre-existing immunity to H1N1 virus or with a live-attenuated influenza vaccine showed protection against a lethal bovine-derived HPAI H5N1 viral challenge . Notably, ferrets with mixed immunity also demonstrated protection against a feline-derived H5N1 virus, independent of cross-reactive neutralization titers , but antibodies to whole virus were observed. To investigate protective factors, we conducted T cell epitope mapping using published H1N1 viral sequences and found high conservation of key T cell epitopes in the bovine HPAI H5N1 strain . Depletion of T cells in mice prior to and during primary H1N1 infection impacted cross-protective antibodies to H5N1 virus, with CD4 depletion increasing mortality and CD8 depletion mildly impacting morbidity upon H5N1 viral challenge. This underscores the need to investigate memory T cell responses...

  Abstract Influenza A viruses exhibit broad host tropism, infecting multiple species including humans, avian species, and swine. Swine influenza virus (SIV), while primarily circulating in porcine populations , demonstrates zoonotic potential with sporadic human infections . In this investigation, we identified two H1N1 subtype swine influenza A virus strains designated A/swine/China/SD6591/2019(H1N1) (abbreviated SD6591) and A/swine/China/SD6592/2019(H1N1) (abbreviated SD6592) in Shandong Province , China. The GenBank accession numbers of the SD6591 viral gene segments are PV464931-PV464938, and the GenBank accession numbers corresponding to each of the eight SD6592 viral gene segments are PV464939-PV464946. Phylogenetic and recombination analyses suggest potential evolutionary differences between the isolates. SD6591 displayed a unique triple-reassortant genotype : comparative nucleotide homology assessments demonstrated that the PB2, PB1, NP, NA, HA, and NEP genes shared the hi...

  ABSTRACT Multiple genes are involved in the pathogenicity of influenza A virus . Our previous study reported two naturally occurring amino acid mutations in the polymerase acidic (PA) protein as crucial determinants of the virulence of Eurasian avian-like H1N1 (EA H1N1) influenza viruses. PA-X, an accessory protein encoded by the PA gene , is thought to play a role in viral pathogenicity and regulation of host immune response , but its specific function remains unclear. In this study, we found that two genetically similar EA H1N1 influenza viruses , A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), induced significantly different suppression levels of host protein synthesis . The difference in host shutoff activity induced by PA-X protein was the key factor affecting the inhibition of host gene expression . Loss of PA-X expression significantly reduced its host shutoff activity , thereby enhancing host antiviral immune response . PA-X deficiency had no appa...

  Abstract In a new study, Zhao et al. (2025) obtain 959 whole genome sequences of H1N1 subtype swine influenza virus (SIV) isolated from China . Their analysis of the sequences , isolated between 1977 and 2020, reveals how H1N1 lineages have co-evolved and contributed to instances of zoonotic transmission within the region. This study’s findings characterize the long-term evolutionary effects of frequent viral reassortment in SIV and highlight its potential to drive future pandemics. Source:  Link:  https://academic.oup.com/evolut/advance-article/doi/10.1093/evolut/qpaf262/8400336 ____

  Influenza at the human-animal interface  Summary and risk assessment, from 6 November to 19 December 2025 {1} -- New human cases {1,2}:  - From 6 November to 19 December 2025, based on reporting date , the detection of influenza A( H5N1 ) in one human , A( H5N5 ) in one human , A( H9N2 ) in seven humans , and an influenza A( H1N1 ) variant virus in one human were reported officially.  - In addition , one human case of infection with an influenza A( H1N2 ) variant virus was detected.  -- Circulation of influenza viruses with zoonotic potential in animals :  - High pathogenicity avian influenza (HPAI) events in poultry and non-poultry animal species continue to be reported to the World Organisation for Animal Health (WOAH).{3}  - The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  - Additionally, low pathogenicity avian influenza viruses as well a...

  Abstract Farmed mink are frequently exposed to circulating influenza A viruses (IAVs), as confirmed by viral isolation and serological evidence. Previous work reveals that naïve mink serve as susceptible hosts for both avian and human influenza strains , highlighting their potential role in influenza ecology . In this study, we investigated whether farmed mink naturally pre-exposed to H9 retain the capacity to serve as “mixing vessels” for reassorting human and avian IAVs. Our results demonstrate that they remain fully susceptible and permissive to infection by both avian H6N6 and human H1N1 influenza strains . Notably, efficient transmission of these viruses occurred among farmed mink, confirming their potential to sustain viral exchange . These findings indicate that farmed mink represent highly permissive hosts capable of facilitating reassortment between circulating human and avian IAVs. Given this risk, current mink farming practices may substantially increase the likelihood...

  10 December 2025 Situation at a glance Seasonal influenza (‘the flu’) is an acute respiratory infection caused by influenza viruses that circulate globally and year-round.  It can cause illness ranging from mild to severe , sometimes resulting in hospitalization or death.  Seasonal influenza activity has increased globally in recent months, with an increased proportion of seasonal influenza A(H3N2) viruses being detected.  This rise coincides with the onset of winter in the northern hemisphere and an increase in acute respiratory infections caused by influenza and other respiratory viruses typically observed at this time of year.  Although global activity remains within expected seasonal ranges , early increases and higher activity than typical at this time of year have been observed in some regions.  Seasonal influenza viruses, including A(H3N2) viruses, continually evolve over time.  Since August 2025, there has been a rapid increase of A(H3N2) J.2...