#Haemagglutinin 162-164 #deletions enhance #influenza B/Victoria virus #fitness and #virulence in vivo

 

Abstract

Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans, only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics, yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics, we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3, which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice. Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures. These findings reveal that specific combinations of HA deletions and substitutions confer pronounced fitness advantages to emerging variants, driving global selective sweeps, evolutionary success and long-term persistence of B/Victoria lineage, and posing challenges for vaccine efficacy and influenza control.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institutes of Health, 75N93021C00016

Ministry of Health Singapore, CS-IRG/MOH-000374

Ministry of Health Singapore, OF-LCG/MOH-000505-05

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.08.698527v1

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History of Mass Transportation: The Fiat FS ETR.401 Electric Multiple Unit

 

Di maurizio messa - Flickr: FS ETR401, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=20276434

Source: 

Link: https://it.wikipedia.org/wiki/Fiat_Ferroviaria

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#Pathogenesis and #Research #Models of Acute #Influenza-Associated #Encephalitis / #Encephalopathy: An Update

 

Abstract

Influenza-associated encephalitis/encephalopathy (IAE) is a severe neurological complication characterized by central nervous system dysfunction and structural damage following influenza virus infection. Predominantly affecting infants and young children, IAE exhibits its highest incidence in those under five years of age. Key clinical manifestations of IAE include acute seizures, sudden high fever, and impaired consciousness, frequently progressing to coma. Neuroimaging, particularly magnetic resonance imaging (MRI), often reveals multifocal brain lesions involving multiple brain regions, including the cerebellum, brainstem, and corpus callosum. The prognosis of IAE is poor, with a mortality rate reaching 30%. Current diagnosis relies heavily on clinical presentation and characteristic neuroimaging findings, as the precise pathogenesis of IAE remains elusive. While various research models, including cell lines, brain organoids, and animal models, have been developed to recapitulate IAE features, significant limitations persist in modeling the core clinical pathophysiology observed in pediatric patients, necessitating further model refinement. This review synthesizes the clinical spectrum of IAE, summarizes progress in understanding its pathogenesis, and critically evaluates existing research models. We aim to provide a foundation for utilizing experimental approaches to elucidate IAE mechanisms and identify potential therapeutic strategies.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/95

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#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, Jan. 8 '26)

 

{Excerpt}

Time Period: December 28, 2025 - January 03, 2026

-- H5 Detection: 3 site(s) (0.7%)

-- No Detection: 428 site(s) (99.3%)

-- No samples in last week: 111 site(s)

(...)

Source: 

Link: https://www.cdc.gov/nwss/rv/wwd-h5.html

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#Sweden - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{A barnacle goose} By Andreas Trepte - Own work, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=32487518

___

In accordance with the WOAH Terrestrial Animal Health Code, Article 10.4.1, point 4, this outbreak does not change the disease-free status of Sweden as these are wild birds or birds kept in a single household, and therefore do not fall within the WOAH definition of poultry.

{Sjöbo Region} A barnacle goose was killed. It was sent to the Swedish Veterinary Agency for laboratory analysis as part of the national surveillance program for avian influenza.

Source: 

Link: https://wahis.woah.org/#/in-review/7180

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#Philippines - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 

Affected avian species were grazing ducks in Davao del Sur Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7105

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One confirmed and one potential #human case of #influenza #H5N1 detected through an expanded subtyping protocol

 

ABSTRACT

Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes individuals with known animal exposures, potentially missing community-acquired infections. To address this gap, we implemented universal H5 subtyping of all influenza A-positive respiratory samples collected within our hospital system, regardless of patient exposure history. Between August 2024 and April 2025, we subtyped 4,488 influenza A-positive samples and identified two cases positive for H5 RNA in Alameda County, California, USA. The first case was a 14-month-old girl with mild respiratory symptoms and no H5N1 exposure risks; sequencing of the sample revealed an H5 gene closely related to clade 2.3.4.4b, genotype B3.13 viruses circulating in U.S. dairies. The second case was a 79-year-old male, also with no known exposures, whose sample reproducibly tested positive with a high cycle threshold value but could not be confirmed by public health laboratories. Both patients had evidence of co-infection with other common respiratory viruses. These findings, while requiring cautious interpretation due to low virus levels and the presence of potential confounding factors, highlight limitations in exposure-based testing and demonstrate the potential for cryptic H5N1 circulation. This report underscores that broader, geographically targeted surveillance may be a critical tool for early detection of potential community transmission of pandemic-capable pathogens.

Source: 

Link: https://journals.asm.org/doi/10.1128/asmcr.00165-25

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Within-host adaptive #evolution is limited by genetic #drift in experimental #human #influenza A virus #infections

 

Abstract

Selection of advantageous mutations drives the emergence of dominant variants during seasonal influenza epidemics. However, within-host detection of such variants remains rare, limiting our understanding of how selection operates at the scale of individual hosts. In this study, we used a controlled human infection model to examine the within-host evolutionary dynamics in thirteen participants intranasally infected with a seasonal H3N2 influenza A virus. Although this clinical trial is ongoing, our work represents a pre-planned, interim, exploratory analysis. Results in this system were contrasted with those observed in a ferret model of infection. The inoculum, used in both humans and ferrets, carried standing diversity that enabled evaluation of variant trajectories during infection. Although the dynamics were variable among participants, in humans, the minor variants in the PA and NP gene segments tended to increase in frequency as infection progressed. Variant dynamics were more consistent among ferrets but showed differences from humans in the fate of the minor NP allele. Based on these observations, we fit a population genetic model to longitudinal measurements of variant frequencies. Estimates of variant selection coefficients and effective viral population sizes indicated that in humans the two minor variants had a selective advantage over the major variants, but genetic drift was strong, limiting the efficiency of selection. In ferrets, the PA minor variant also was estimated to have a selective advantage, while the NP minor variant was estimated to have a selective disadvantage. Moreover, effective viral population sizes were estimated to be considerably higher in ferrets than in humans, indicating that genetic drift was weaker in ferrets. Our analyses reveal differing selective environments acting on influenza viruses in human and ferret hosts and indicate that selection at the within-host level is weakened by genetic drift.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.07.698006v1

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#Poland - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Follow up report 2

 

Poultry farms in Podlaskie Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7177

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#Lassa fever #symptomatology, viral dynamics, and host immune response (PREPARE): a prospective, observational cohort study in #Liberia

 

Summary

Background

Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond. LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths. With over 32 reported cases of Lassa fever imported into non-endemic countries—one-third of which were fatal—the importance of enhanced detection and management of Lassa fever extends beyond west Africa.

Methods

The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia. Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever.

Findings

From July 10, 2018, to Aug 12, 2024, a total of 435 participants were enrolled, including 362 admitted with a febrile illness and 73 who were directly admitted with clinical suspicion for Lassa fever. Lassa fever was diagnosed by plasma LASV RT-PCR in 41 (11%) of 362 febrile participants and 47 (64%) of 73 participants directly admitted with suspected Lassa fever, resulting in a total of 88 cases of confirmed Lassa fever. At entry, anorexia (71 [81%] of 88 vs 178 [51%] of 347), severe fatigue or weakness (63 [72%] vs 178 [51%]), and nausea or vomiting (39 [44%] vs 95 [27%]) were more likely to be reported by participants with Lassa fever than by participants who tested LASV RNA negative. Among the participants with Lassa fever, 11 (13%) of 88 died after admission. Mental status changes, seizures, acute kidney failure, hyperkalaemia, and metabolic acidosis were more frequent in patients with Lassa fever who died than in patients who survived. Median cycle threshold values at study entry for glycoprotein complex gene (GPC) or polymerase gene (L) were lower in those who died (GPC cycle threshold 22·4 [IQR 20·0–27·9]; L cycle threshold 21·7 [19·0–27·7]) than in those who survived (GPC cycle threshold 31·5 [28·0–33·9]; L cycle threshold 32·3 [28·0–33·9]). Among the 70 participants with Lassa fever who consented to longitudinal follow-up through their hospitalisation, seven died and these participants tended to have lower cycle threshold values and lower IgM and IgG LASV responses compared with survivors.

Interpretation

In a region of Liberia where it is endemic, Lassa fever is a prevalent cause of morbidity and mortality. Several symptoms were more likely in those with Lassa fever but overlap with those caused by other common infectious diseases. Compared with survivors, those who died during hospitalisation for Lassa fever tended to have evidence of organ dysfunction along with higher viral loads at study entry and during follow-up and lower antibody levels during their illness, suggesting a muted humoral immune response might be a factor in the development of severe Lassa fever.

Funding

US National Institute of Allergy and Infectious Diseases and National Institutes of Health.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00725-X/abstract?rss=yes

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Adjuvanted #influenza #vaccination increases pre-existing #H5N1 cross-reactive #antibodies

 

Abstract

Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic. Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States. These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies. In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodies. Additionally, we find that AS03-adjuvanted pandemic H1N1 vaccination increases H5N1 cross-reactive antibodies significantly in a pandemic H1N1 immunologically partially naïve population. Furthermore, we show that immune imprinting causes distinct H5N1 cross-reactive antibody patterns pre-vaccination.

Source: 

Link: https://www.nature.com/articles/s41467-025-68137-x

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Structural basis for #human #DPP4 #receptor recognition by #MERS-like #coronaviruses 2014-422 and GX2012

 

Abstract

Since its emergence in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has posed a significant threat to human health. Recently, novel MERS-like coronaviruses with the potential for cross-species transmission have been identified. In this study, we focused on two newly isolated bat strains with putative health concern: BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012). We determined the cryo-EM structures of the spike glycoprotein trimer in the closed state for these two viruses. These structures display a more compact conformation compared to MERS-CoV spike. Biochemical characterization demonstrates that the spike receptor-binding domains (RBDs) of 2014-422 and GX2012 can bind to human dipeptidyl peptidase 4 (hDPP4). To investigate the structural determinants of pseudovirus infection, we solved the cryo-EM structures of 2014-422 RBD-hDPP4 and GX2012 RBD-hDPP4 complexes. The binding mode of the complex is conserved, but the angle of the RBD binding undergoes significant tilting. Detailed structural analysis reveals that an additional residue at position 514 interacts with the N321 glycan in hDPP4, altering the binding angle and thus influencing receptor recognition. These findings offer valuable insights into the receptor utilization of Merbecovirus and provide a structural basis for future surveillance efforts.

Author summary

Two MERS-like coronaviruses, BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012), have recently emerged as potential zoonotic threats. In this study, we provide a detailed structural analysis of these two viruses, focusing on their spike proteins and interactions with human Dipeptidyl Peptidase 4 (hDPP4), the receptor used by MERS-CoV. Using cryo-electron microscopy (cryo-EM), we determined high-resolution structures of 2014-422 and GX2012 spike glycoproteins in their closed conformations. Our results show that GX2012 mediates efficient pseudovirus entry into human cells, whereas 2014-422 shows markedly reduced entry efficiency. This difference is linked to structural variations, including a unique residue at position 514 in both viruses that affects the RBD binding angle and receptor recognition. Together, these findings provide key insights into the structural basis of receptor usage by MERS-like coronaviruses and suggest that HKU4r-CoVs may acquire the ability to infect human cells through two evolutionary routes: within bats and through pangolins as intermediate hosts.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013792

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#USA, #Massachusetts reports three #pediatric #deaths due to seasonal #influenza so far (DoH, Jan. 8 '26)

 

Boston — The Massachusetts Department of Public Health (DPH) is reporting very high and rising levels of influenza activity statewide as the Commonwealth moves through peak flu season. 

Thousands of residents have become ill, forcing them to miss work, school, and other activities. 

Many are experiencing serious complications, leading to increased visits to urgent care centers and emergency departments, and high levels of hospitalization. 

The current widespread burden of illness underscores the importance of taking preventive measures, especially vaccination, to reduce severe disease and protect individuals, families, and communities.

Tragically, influenza has already been reported to be associated with the deaths of three pediatric patients in Massachusetts during recent weeks. 

In addition, there have been 29 adult influenza deaths reported so far this season. 

While COVID-19 and respiratory syncytial virus (RSV) rates currently remain low, cases of both illnesses are beginning to rise. 

DPH is reviewing two possible COVID-19-associated deaths and one RSV-associated death in individuals younger than 18 years. 

“This is a moment for clarity, urgency, and action,” said Public Health Commissioner Robbie Goldstein, MD, PhD. 

“These viruses are serious, dangerous, and life-threatening. We are seeing children who are seriously ill, families grieving devastating losses, and hospitals under capacity strain. There is a simple, effective, and available way to address these concerns: vaccines. They can prevent serious illness and hospitalization. And they save lives. If you have not yet been vaccinated against flu or COVID-19 this season, now is the time. It is not too late. Choosing vaccination is choosing to protect yourself, your family, your friends, your colleagues, and your community.”

Hospitals across Massachusetts are continuing to see high numbers of patients seeking care for respiratory illness. 

Each day last week, there were nearly 9,000 emergency department visits statewide, with approximately one-quarter of those related to acute respiratory illness, including flu, COVID-19, and RSV. 

Some regions in the state reported challenging hospital capacity levels exceeding 90% in medical-surgical units, largely related to influenza. 

DPH urges everyone 6 months of age and older to stay up to date on flu and COVID-19 vaccinations. These annual shots can be given at the same visit and are available from local boards of health, community health centers, pharmacies, and many health care providers.

Vaccination is especially important for people at higher risk of severe disease, including adults age 65 years and older, children between 6 months and 2 years old, people with chronic respiratory conditions or heart disease, individuals who are immunocompromised, and people who are pregnant. Vaccination also helps protect family members, coworkers, and others in the community who may be more vulnerable to serious illness. 

For RSV, one-time immunization is recommended for adults age 75 and older, those aged 50-74 who have conditions that put them at increased risk, and people who are pregnant. 

For infants and children, parents should talk with their child’s health care provider about RSV immunization. It is recommended that infants younger than 8 months be immunized if the birth parent did not receive the RSV shot during pregnancy. Children between 8 and 19 months who are at increased risk because of certain pulmonary or immune system disorders should also be immunized. 

In Massachusetts, vaccines are covered by insurance and are available at no cost for almost all adults. All vaccines for individuals younger than 18 years are supplied free of charge to health care providers through the state’s universal childhood immunization program. 

For those who begin to experience flu symptoms – which include high fever, chills, muscle aches, headache, extreme fatigue, cough, sore throat, and congestion – antiviral medications, such as oseltamivir (Tamiflu), are available by prescription. When started early, these medications can significantly reduce the severity of illness. Parents are encouraged to seek medical advice promptly if they or their children develop flu-like symptoms.

Spending time indoors and around larger groups increases the likelihood of exposure to respiratory viruses. The following everyday measures can help prevent illness:

-- Stay up to date on flu and COVID-19 vaccinations

-- Wash hands frequently with soap and water

-- Stay home when sick

-- Cover coughs and sneezes

-- Consider wearing a mask in crowded indoor settings, especially if you or a loved one is at higher risk.

DPH continues to closely monitor respiratory activity and hospital capacity across Massachusetts. Up-to-date data are available on the DPH respiratory virus dashboard.  

Source: 

Link: https://www.mass.gov/news/massachusetts-reports-very-high-flu-activity-with-cases-climbing

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Natural #H5N1 #immunity in dairy #cows is durable and cross-protective but non-sterilizing

 

Abstract

Ongoing transmission of influenza A virus (H5N1) in U.S. dairy cattle threatens both animal and human health, underscoring the need to understand the durability of host immunity against reinfection with evolving genotypes. We challenged naive and convalescent cows, infected one year prior with H5N1 genotype B3.13, with either homologous B3.13 or heterologous D1.1 genotype virus. Homologous rechallenge resulted in complete clinical protection with no infectious viral shedding. Conversely, heterologous rechallenge led to transient clinical disease and limited infectious viral shedding. Convalescent cows experienced significantly milder disease than naive cows, which developed severe illness with high viral shedding and required early euthanasia, regardless of the strain. These findings indicate that naturally acquired immunity offers strong protection against severe illness but may allow silent transmission of divergent strains. Therefore, natural herd immunity alone is unlikely to eliminate the virus; controlling H5N1 in cattle will likely require vaccination strategies that address viral evolution.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Centers of Excellence for Influenza Research and Response (CEIRR), 75N93021C00016

National Institute of Allergy and Infectious Diseases, 75N93021C00016

National Institutes of Health, Department of Health and Human Services, 75N93021C00016

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.06.697911v1

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#mRNA-delivered neutralizing #antibodies confer protection against #SARS-CoV-2 in animal #models

 

ABSTRACT

Monoclonal antibodies represent potent biological countermeasures against a wide range of human diseases; however, their clinical application and widespread use are limited by the high cost and complexity of antibody production and manufacturing. The mRNA-lipid nanoparticle (mRNA-LNP) platform offers a versatile strategy for vaccine development and protein-replacement therapies. Since the COVID-19 pandemic, a number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies have been identified, with several granted emergency use authorization for patients. Here, we report the design and generation of mRNA-LNPs encoding two SARS-CoV-2-neutralizing antibodies, 76E1 and LY1404, which, respectively, target the spike protein’s fusion peptide (FP) and receptor-binding domain (RBD). We demonstrated that a single intramuscular administration of these mRNA-LNPs in mice resulted in robust antibody production that sustained in circulation for 7–14 days. Furthermore, we evaluated protective effects of these mRNA-delivered antibodies in animal models and showed that a single IM dose of mRNA-LNPs encoding LY1404 or 76E1 conferred significant protection against multiple SARS-CoV-2 variants, including Omicron BQ.1 and Delta, in mice and hamsters. Collectively, these findings highlight the potential of mRNA-based antibody delivery for rapid prevention or treatment of pathogenic infections.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/jvi.01897-25?af=R

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Intrahost HA #polymorphisms and culture #adaptation shape antigenic profiles of #H3N2 #influenza viruses

 

ABSTRACT

Accurate antigenic characterization of influenza viruses is critical for vaccine strain selection but is often confounded by intrahost genetic diversity and culture-induced adaptations. We analyzed 60 A(H3N2)-positive nasopharyngeal specimens collected during the 2017–2018 influenza season to determine how virus propagation in MDCK cells affects viral genetic and antigenic properties. Deep sequencing revealed frequent genome-wide intrahost polymorphisms, including amino acid variants within major hemagglutinin (HA) antibody-binding sites. Virus propagation imposed rapid purifying selection, markedly reducing intrahost genetic diversity. Serological analyses demonstrated that these selective events altered antigenic properties, indicating that culture adaptation can alter antigenic profiles. To assess the functional impact of HA polymorphisms, we generated mixed viral populations containing defined ratios of HA-160K, HA-160T, and HA-160I variants identified in clinical samples. These reconstituted populations exhibited a continuum of antigenic reactivities, confirming that amino acid polymorphisms drive antigenic heterogeneity among clinical samples. Together, our findings demonstrate that intrahost variation contributes to antigenic diversity in human A(H3N2) clinical specimens and that virus isolation procedures can bias antigenic characterization, underscoring the importance of direct profiling of uncultured clinical material to improve vaccine strain selection accuracy for seasonal human influenza.

IMPORTANCE

Accurate antigenic characterization of influenza viruses is essential for vaccine strain selection, yet routine isolation of viruses in cell culture can introduce genetic changes that obscure the properties of circulating strains. By combining deep sequencing with serological analysis of clinical specimens and cultured isolates, we demonstrate that virus propagation of human seasonal A(H3N2) in MDCK cells imposes strong purifying selection and alters antigenic profiles. Furthermore, we show that minor amino acid polymorphisms present in clinical samples can generate measurable antigenic diversity, emphasizing that natural intrahost variation shapes antigenic outcomes. These findings reveal a critical source of bias in antigenic characterization workflows and underscore the importance of directly assessing uncultured clinical material. Improved understanding of how culture adaptation and intrahost genetic diversity influence antigenic data will advance knowledge of antigenic evolution in circulating influenza viruses and improve the accuracy of vaccine strain selection for human seasonal influenza.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/jvi.01775-25?af=R

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#UK [#Scotland] - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

{Scotland}

A small commercial poultry premise. Samples taken were positive for HPAI H5N1. Birds presented clinical signs prior to testing.

Source: 

Link: https://wahis.woah.org/#/in-review/7173

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#Influenza hemagglutinin subtypes have different #sequence constraints despite sharing extremely similar #structures

 

Abstract

Hemagglutinins (HA) from different influenza A virus subtypes share as little as ~40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ~50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge.

Competing Interest Statement

JDB consults for Apriori Bio, Invivyd, Pfizer, GSK, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to the deep mutational scanning of viral proteins.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, R01AI165821, 75N93021C00015

U.S. National Science Foundation, DGE-2140004

Howard Hughes Medical Institute, https://ror.org/006w34k90

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.05.697808v1

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#Hungary - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

A fattening turkey holding in Csongrád-Csanád Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7172

____

#Adaptation differences and mechanisms of #influenza viruses to ANP32 #proteins across #species

 

ABSTRACT

Avian influenza virus cross-species infection in humans poses a major threat to global public health. Species-specific differences between avian ANP32A and mammalian ANP32 proteins create a natural barrier against viral cross-species infection by directly impairing the functional interaction between the avian-origin viral RNA polymerase and mammalian ANP32 proteins, thereby restricting viral genome replication. The key to overcoming this barrier lies in the adaptation of viral RNA polymerase to host ANP32 family proteins. This mini-review summarizes the mechanisms and variations in influenza virus adaptation to ANP32 proteins across different species. Influenza viruses adapt to species-specific ANP32 proteins through various mutations and display distinct preferences for specific ANP32 family members within the same host. Additionally, alternative splicing variants of ANP32A within a single species further modulate viral RNA polymerase adaptability. Despite this diversity, the underlying interaction mechanism remains conserved: ANP32–polymerase binding is necessary but not sufficient for optimal polymerase activity. This interaction facilitates the formation of asymmetric polymerase dimers and specifically supports viral genome replication, while the step from cRNA to vRNA remains subject to species-specific restrictions. This explains the classic adaptive mechanism of the PB2 E627K mutation, which restores efficient viral genome replication through acid–base pairing with ANP32A. Furthermore, adaptive mutations in emerging strains such as H3N2 canine influenza virus and recent cases of H5N1 in dairy cows underscore the need for continuous viral surveillance and deeper mechanistic studies on virus–ANP32 interactions. Such research is strategically critical for advancing the One Health approach and mitigating future influenza pandemics.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/jvi.01900-25?af=R

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Case Report: #CJD and #diagnosis #challenges: case report and evidence synthesis

 

Abstract

Introduction

Prion diseases are mortal neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD). Due to its heterogenous clinical presentation diagnosis uncertainties are common. In this paper we explore CJD diagnostic challenges focusing on differential diagnosis and diagnostic delays.

Methods

We report a case of a patient who was misclassified and evaluated by several medical specialties before the CJD suspicion. A systematic review of the literature of the CJD case reports focused on the timely and differential diagnosis was carried out in Medline and Embase until May 2023.

Results

Patient with diagnosis was made due to the form of presentation and clinical evolution, neuroimaging and the presence of protein 14-3-3. In systematic review, fifteen articles were selected, who reported 31 cases of CJD with problems in the timely diagnosis and incorrect initial diagnosis, the main initial differential diagnoses were psychiatry exacerbation, myelopathy, epilepsy, stroke, parkinsonism, cerebellar ataxia and autoimmune encephalitis. The most common clinical onset was psychobehavioral disturbances (apathy, confusion and sleep disturbance), extrapyramidal signs and cognitive impairment. The diagnosis delay was from one to eighteen months.

Conclusion

A discussion of the case report and the diagnostic challenges reported in the literature was made. Patients can present a wide range of symptoms. It is recommended to consider CJD for the differential diagnosis in patients with behavioral symptoms, and cognitive impairment.

Source: 

Link: https://f1000research.com/articles/14-425

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#Israel - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

Reproductive ducks. 41 months old. Drop in lay and reduction of water consumption. Gastrointestinal symptoms. HaZafon Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7168

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#Lithuania - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

A wild mute swan in Kauno Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7166

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Development of a multi-species #luciferase-based double #antigen #ELISA for the detection of #antibodies against #Influenza A virus #H5 clade 2.3.4.4b

 

Abstract

The highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 represent a major threat to animal and public health. The current panzootic with H5 clade 2.3.4.4b has caused numerous, widespread outbreaks in various domestic and wild avian species with high mortalities, massive losses and a high frequency of spillover events to unexpected novel mammalian hosts such as dairy cows. The global H5N1 situation raises serious concerns about zoonotic risks due to effective mammal-to-mammal transmission. Therefore, it is critical to increase surveillance intensity of a broadened species range, particularly at the human-animal interface. For this purpose, reliable and cost-effective serological tools that are easy to perform and suitable for high-throughput screenings are critically needed. The newly developed double antigen ELISA format employing a luminescence-based detection technology has demonstrated to comply with such prerequisites. The assay allowed the detection of H5-specific antibodies even early after infection or vaccination in a wide range of birds and mammals including humans. It further demonstrated superior analytical sensitivity and high specificity for antibodies directed against H5 hemagglutinin of clade 2.3.4.4b as no cross-reactivity with other hemagglutinin subtypes was observed. Thus, the assay represents a valuable contribution to existing serological diagnostic tests for a clade-optimized detection of influenza A virus antibodies in a broad range of species.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.05.697617v1

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T cell #immunity to seasonal #Influenza A and #H5N1 viruses in #laboratory #workers receiving annual seasonal Influenza #vaccines

 

{Abstract}

Background: 

Emerging threats such as highly pathogenic influenza strains like H5N1 emphasize the need for vaccines that induce cross-reactive immunity against conserved epitopes. Existing influenza vaccines primarily elicit strain-specific responses, leaving gaps in protection against pandemic subtypes. This study aimed to evaluate T cell responses to seasonal influenza A and H5N1 and compare them to SARS-CoV-2 specific T cell responses to understand differences shaped by distinct exposure histories and vaccination strategies.

Methods: 

T cell responses were assessed in 41 laboratory workers who received annual seasonal influenza vaccines using ELISpot to quantify responses to peptide pools derived from influenza (H1N1 hemagglutinin [HA], H3N2 HA, H5N1 HA, matrix protein 1 [MP1], nucleoprotein [NP]) and SARS-CoV-2 (spike [S2S], nucleocapsid [S2N]). Ten-day expansion assays were used to evaluate functional cross-reactivity between H1, H3, and H5 HA. Intracellular cytokine staining was performed to assess antigen-specific T cell functionality. We used the IFN-γ ELISpot assay and intracellular cytokine staining to evaluate T cell responses to H5N1 HA peptides and assessed cross-reactivity and functional similarity in H1N1 HA-expanded cells.

Results: 

The percentage of individuals with effector T cell responses to influenza peptide pools, was markedly lower than the percentage of individuals with S2S-specific T cells. However, HA-specific memory cells that cross-recognized H1, H3, and H5 HA were present in many individuals. T cells expanded with H1 or H5 HA proteins cross-recognized homologous epitopes in the 2 proteins and cytokine production profiles were comparable between H1- and H5-expanded T cells.

Conclusion: 

These results highlight the potential for influenza vaccines to elicit cross-reactive immunity against H5N1 viruses. These findings also demonstrate differences between T cell responses to influenza and SARS-CoV-2, highlighting distinct immune profiles that could inform future vaccine strategies.

Source: 

Link: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1718805/full

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#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, Jan. 5 '26)

 

{Excerpt}

Time Period: December 21, 2025 - December 27, 2025

-- H5 Detection: 4 site(s) (1.1%)

-- No Detection: 359 site(s) (98.9%)

-- No samples in last week: 168 site(s)

(...)

Source: 

Link: https://www.cdc.gov/nwss/rv/wwd-h5.html

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High pathogenicity avian #influenza virus #H5N1 clade 2.3.4.4b in #Antarctica: Multiple Introductions and the First Confirmed Infection of Ice-Dependent #Seals

 

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b has expanded rapidly across the Southern Ocean since 2023, causing extensive mortality in sub-Antarctic wildlife. Yet its penetration into Antarctica and impacts on ice-dependent species remain poorly resolved primarily due to surveillance constraints. We report the first confirmed H5N1 infection in an Antarctic ice-dependent seal (crabeater seal; Lobodon carcinophaga) and document mortality of crabeater seals across the northern Weddell Sea during November-December 2024. Combining genomic, serological and observational data across nine species, we detected H5N1 RNA in a crabeater seal and a kelp gull (Larus dominicanus), and recovered complete HA, NA and M2 gene sequences from both. Phylogenetic analyses allowed us to identify at least two independent introductions of HPAI H5N1 clade 2.3.4.4b into the northern Antarctic Peninsula region. Serology provided strong evidence of prior exposure in scavenging birds, but no detectable H5 immunity in penguins or pinnipeds. Together, the results demonstrate ongoing novel viral incursions into Antarctica, likely facilitated by at-sea processes e.g. animal interactions on ice floes, that remain invisible to land-based surveillance. These findings highlight the vulnerability of ice-dependent pinnipeds to HPAI H5N1 clade 2.3.4.4b and the urgent need for expanded integrated Antarctic monitoring frameworks that pair serology, opportunistic carcass sampling and genomic sequencing.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Rolex-National Geographic Perpetual Planet Expeditions

Schmidt Oceans Institute

Geoffrey Evans Trust

Kenneth C. Griffin

Griffin Catalyst

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.04.697571v1

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#Poland - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

A poultry farm in Lubelskie Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7162

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#India - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

{Kerala}

1) The outbreak was detected in ducks within an integrated rice–duck farming system.

2) The outbreak was detected in ducks within an integrated rice–duck farming system.

3) The outbreak was detected in ducks within an integrated rice–duck farming system.

4) The outbreak was detected in ducks within an integrated rice–duck farming system.

5) The outbreak was detected in ducks within an integrated rice–duck farming system.

6) The outbreak was detected in ducks within an integrated rice–duck farming system.

7) The outbreak was detected in ducks within an integrated rice–duck farming system.

8, 9 & 10) Poultry farms.

Source: 

Link: https://wahis.woah.org/#/in-review/7161

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