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lördag 5 juli 2025

Fokusoin H5N1 viruksen hemaglutiniinin HA rakenteeseen PubMed haku

 

281 results

Single-Cell Analysis of Host Responses in Bovine Milk Somatic Cells (bMSCs) Following HPAIV Bovine H5N1 Influenza Exposure.
Singh G, Kafle S, Assato P, Goraya M, Morozov I, Richt JA. Viruses. 2025 Jun 3;17(6):811. doi: 10.3390/v17060811. PMID: 40573402 Free PMC article.
Unlike previously described subclinical influenza A virus (IAV) infections in cattle, H5N1 infection induced severe clinical symptoms, including respiratory distress, mastitis, and abnormal milk production. To understand the host immune responses and changes, particularly …
Design, Synthesis and In Vivo Evaluation of a Candidate Fusion Epitopic Construct Vaccine Based on M2e, HA1, HA2, NA and NP Fragments of the Highly Pathogenic Avian H5N1 Influenza Virus.
Hamidi A, Farzin H, Haghparast A. Arch Razi Inst. 2024 Aug 1;79(4):849-856. doi: 10.32592/ARI.2024.79.4.849. eCollection 2024 Aug. PMID: 40256578 Free PMC article.
One highly regarded solution to this problem is to design and production of recombinant vaccines using the conserved peptide of influenza viruses. A search of international databases yielded the peptide sequence of the M2e fragment of H5N1 viruses isol …
Conformational Variability Prediction of Influenza Virus Hemagglutinins with Amino Acid Mutations Using Supersecondary Structure Code.
Izumi H. Methods Mol Biol. 2025;2870:63-78. doi: 10.1007/978-1-0716-4213-9_5. PMID: 39543031
The deep neural network-based conformational variability prediction system of protein structures (SSSCPreds) can simultaneously predict locations of protein flexibility or rigidity and the shapes of those regions with high accuracy. The sequence flexibility/rigidity map ob …
Proper development of long-lived memory CD4 T cells requires HLA-DO function.
Song N, Welsh RA, Sadegh-Nasseri S. Front Immunol. 2023 Oct 16;14:1277609. doi: 10.3389/fimmu.2023.1277609. eCollection 2023. PMID: 37908352 Free PMC article.
INTRODUCTION: HLA-DO (DO) is an accessory protein that binds DM for trafficking to MIIC and has peptide editing functions. DO is mainly expressed in thymic medulla and B cells. Using biochemical experiments, our lab has discovered that DO has differential effects on editin …
The heterophilicic epitopes in conserved HA regions of human and avian influenza viruses can produce antibodies that bound to kidney tissue.
Guo CY, Jin ZK, Feng Q, Feng YM, Sun LJ, Xu CX, Zhang YL. Microb Pathog. 2023 Dec;185:106331. doi: 10.1016/j.micpath.2023.106331. Epub 2023 Sep 9. PMID: 37678657 Free article.
The purpose of this study was to analyze the relationship between heterophilic epitopes on H5N1 hemagglutinin (HA) and disease. The monoclonal antibody (mAb) against H5N1 was prepared, mAbs binding to human kidney tissue were screened, and the reactivities of mAbs w …
Boost immunizations with NA-derived peptide conjugates achieve induction of NA inhibition antibodies and heterologous influenza protections.
Liu DJ, Liu CC, Zhong XQ, Wu X, Zhang HH, Lu SW, Shen ZL, Song WW, Zhao SL, Peng YS, Zheng HP, Wan MY, Chen YQ, Deng L. Cell Rep. 2023 Jul 25;42(7):112766. doi: 10.1016/j.celrep.2023.112766. Epub 2023 Jul 7. PMID: 37421618 Free article.
To overcome this, we rationally select the highly conserved peptides from the consensus amino acid sequence of the globular head domains of neuraminidase. ...Overall, this study provides proof of concept for a peptide-based sequential immunization strategy fo …
Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza.
Russo G, Crispino E, Maleki A, Di Salvatore V, Stanco F, Pappalardo F. BMC Bioinformatics. 2023 Jun 5;24(1):231. doi: 10.1186/s12859-023-05374-1. PMID: 37271819 Free PMC article.
When it was first introduced in 2000, reverse vaccinology was defined as an in silico approach that begins with the pathogen's genomic sequence. It concludes with a list of potential proteins with a possible, but not necessarily, list of peptide candidates that need …
Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.
Bull MB, Gu H, Ma FNL, Perera LP, Poon LLM, Valkenburg SA. Sci Adv. 2022 Apr 8;8(14):eabl5209. doi: 10.1126/sciadv.abl5209. Epub 2022 Apr 6. PMID: 35385318 Free PMC article.
To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral vectored vac …
Infiltration of inflammatory macrophages and neutrophils and widespread pyroptosis in lung drive influenza lethality in nonhuman primates.
Corry J, Kettenburg G, Upadhyay AA, Wallace M, Marti MM, Wonderlich ER, Bissel SJ, Goss K, Sturgeon TJ, Watkins SC, Reed DS, Bosinger SE, Barratt-Boyes SM. PLoS Pathog. 2022 Mar 10;18(3):e1010395. doi: 10.1371/journal.ppat.1010395. eCollection 2022 Mar. PMID: 35271686 Free PMC article.
Here we used a unique translational model of lethal H5N1 influenza in cynomolgus macaques that utilizes inhalation of small-particle virus aerosols to define mechanisms driving lethal disease. RNA sequencing of lung tissue revealed an intense interferon response wit …
Transcriptomic Profiling of Mouse Mast Cells upon Pathogenic Avian H5N1 and Pandemic H1N1 Influenza a Virus Infection.
Tang Y, Wu H, Huo C, Zou S, Hu Y, Yang H. Viruses. 2022 Jan 29;14(2):292. doi: 10.3390/v14020292. PMID: 35215885 Free PMC article.
To gain further insights into the host cellular responses of mouse mast cells with influenza A virus infection, such as the highly pathogenic avian influenza A virus H5N1 and the human pandemic influenza A H1N1, we employed high-throughput RNA sequencing to identify …

Lintuinfluenssa HPAI H5N1 viruksen HA-peptidin pilkkoutumiskohdan motiivi

 https://pmc.ncbi.nlm.nih.gov/articles/PMC5057330/

. 2015 Oct 15;25(6):406–430. doi: 10.1002/rmv.1846

Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

PMCID: PMC5057330  PMID: 26467906
  • HA rakenteen Sveitsin malli  https://swissmodel.expasy.org/repository/uniprot/D9I6N5
  •  https://swissmodel.expasy.org/repository/uniprot/D9I6N5

    Hemagglutinin Q5EP31 (Identical to D9I6N5) UniProtKBInterPro

    Toggle Identical (ACE)

    Q5EP31
    6cfg.(ACE)
    Q5EP31
    6cfg.(ACE)
    Q5EP31
    6cfg.(ACE)
    Q5EP31
    6cfg.(ACE)
    Q5EP31
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    Q5EP31
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    Q5EP31
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    Q5EP31
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    Q5EP31
    6cfg.(ACE)
    DQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKKHNGK56
    DQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKKHNGK44
    LCDLDGVKPLILRDCSVAGWLLGNPMCDEFINVPEWSYIV96
    LCDLDGVKPLILRDCSVAGWLLGNPMCDEFINVPEWSYIV84
    EKANPVNDLCYPGDFNDYEELKHLLSRINHFEKIQIIPKS136
    EKANPVNDLCYPGDFNDYEELKHLLSRINHFEKIQIIPKS124
    SWSSHEASLGVSSACPYQGKSSFFRNVVWLIKKNSTYPTI176
    SWSSHEASLGVSSACPYQGKSSFFRNVVWLIKKNSTYPTI164
    KRSYNNTNQEDLLVLWGIHHPNDAAEQTKLYQNPTTYISV216
    KRSYNNTNQEDLLVLWGIHHPNDAAEQTKLYQNPTTYISV204
    GTSTLNQRLVPRIATRSKVNGQSGRMEFFWTILKPNDAIN256
    GTSTLNQRLVPRIATRSKVNGQSGRMEFFWTILKPNDAIN244
    FESNGNFIAPEYAYKIVKKGDSTIMKSELEYGNCNTKCQT296
    FESNGNFIAPEYAYKIVKKGDSTIMKSELEYGNCNTKCQT284
    PMGAINSSMPFHNIHPLTIGECPKYVKSNRLVLATGLRNS336
    PMGAINSSMPFHNIHPLTIGECPKYVKSNRLVLATGLRNS324
    P337
    P

     

    Hemagglutinin A8UDR1 UniProtKBInterPro

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    A8UDR1
    6cfg.(BDF)
    A8UDR1
    6cfg.(BDF)
    A8UDR1
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    GLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKES382
    GLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKES40
    TQKAIDGVTNKVNSIIDKMNTQFEAVGREFNNLERRIENL422
    TQKAIDGVTNKVNSIIDKMNTQFEAVGREFNNLERRIENL80
    NKKMEDGFLDVWTYNAELLVLMENERTLDFHDSNVKNLYD462
    NKKMEDGFLDVWTYNAELLVLMENERTLDFHDSNVKNLYD120
    KVRLQLRDNAKELGNGCFEFYHKCDNECMESVRNGTYDYP502
    KVRLQLRDNAKELGNGCFEFYHKCDNECMESVRNGTYDYP160
    QYSEEARLKREEIS516
    QYSEEARLKREEIS174

    USA:n ihmisissä ilmennyt A H5N1 influenssavirus infektio. Virusten riskien arvioimisesta IRAT

     https://www.cdc.gov/pandemic-flu/php/monitoring/irat-virus-summaries.html

    Public Health

    Results of Influenza Risk Assessment Tool

    At a glance

    • The Influenza Risk Assessment Tool (IRAT) is a CDC evaluation tool developed with assistance from global animal and human health influenza experts.
    • The IRAT is used to assess the potential pandemic risk of influenza A viruses that are not currently circulating in people.
    • This latest IRAT assessed two recent clade 2.3.4.4b avian influenza A(H5N1) viruses: A/California/147/2024 and A/Washington/239/2024.
    • These viruses scored in the "moderate risk" category for potential emergence and public health impact, similar to previous assessments of earlier clade 2.3.4.4b avian influenza A(H5N1) viruses. These results validate the proactive, coordinated U.S. government response.
    • The IRAT does not assess the immediate risk to the public's health, which is unchanged and remains low, and it does not predict future pandemics.

     

    ... jatkoa (3) (paradigman muutos vai huomaamatta jäänyt evoluutio

     

    Influenza viruses spill over periodically from their primordial reservoirs (aquatic fowls) to the intermediate/secondary hosts to facilitate better adaptation and transmission and some of these hosts must remain as permanent niches for sustained IAV transmission. Other than birds, influenza A affects diverse mammalian populations such as pigs, seals, horses, dogs, cats, wild cats, minks, whales, and humans.
     
     The global pandemic of 2009 caused by swine-origin H1N1 was reported in swine, turkey, dogs, and cat [9,10,11,12,13,14].
     
     Over the last few years, influenza infection landscape has widened to include new mammalian hosts such as bats, seals, and whales [6,15,16,17,18].
     
     Humans are the intermediate hosts for many diseases and zoonotic infections can occur in two ways: (1) isolated, dead-end infections which fail to establish and adapt as in the case of Ebola and hantaviruses (2) virus adapts and establishes in the intermediate or secondary hosts, and also sustain horizontal transmission, as in influenza [19]. 
     
     Such stable host-switch events lead to strong adaptations (ex. H5N1 and H9N2) which can resist the evolutionary pressure or the antagonistic environment posed by the novel hosts [20,21,22]. 
     
    The factors that govern the virulence, pathogenicity and transmission of influenza viruses could be multifactorial including both viral as well as host factors. Host factors such as availability of the receptors, the presence of host innate immune and other cellular factors, population size and its interconnectivity all govern the sustainability of influenza transmission [23]. 
     
    Influenza viral determinants undergo adaptive mutations, to expand or to limit the host range. Among the viral factors, HA glycoprotein is the primary factor determining the host range and interspecies transmission. Other viral proteins such as NP, PB2, and NS1 have also been involved in host range restriction and adaptation [24]. 
     
     For example, avian influenza polymerase possesses a limited function in human hosts and hence host-specific genetic changes have occurred to the polymerase subunits and NP during natural evolution. 
     
    Though uncommon in recent times, IAV has been reported in ruminant species in the past. However, a tight host genetic bottleneck might have played a major role in the evolution, preventing the adaptive mutations necessary for the sustained transmission cycles in a novel host.
     
     Interestingly, the recently emerged influenza D, for which cattle are considered to be the primary reservoir, is widespread in cattle herds across the world. 
     
    In this review, we conducted a comprehensive search of the available scientific reports/journal articles on influenza over the last century, with reference to bovine species, to understand the timeline of bovine IAV incidences with respect to human pandemics and epidemics, natural and experimental infections, seroepidemiological studies, and the role of bovine cellular and host factors in the evolution of influenza.

    2. Literature Search Strategy:  Katso lähde artikkeli!

    2019 Jun 17;11(6):561. doi: 10.3390/v11060561

    PMCID: PMC6631717  PMID: 31213032Abstract

    jatkoa...(2) perustavaa olennaista yleistietoa influenssoista

     Influenza viruses belong to Orthomyxoviridae family and are negative-sense single-stranded RNA viruses causing acute respiratory disease in a multitude of hosts all over the world. Influenza viruses were recognized as early as the 16th century and the first pandemic officially documented was in 1580 [1]. 

    Influenza viruses evolved to form mainly four types: alphainfluenza virus (influenza A), betainfluenza (influenza B), gammainfluenza (influenza C), and deltainfluenza (influenza D) which again diverged to subtypes and lineages, affecting multiple mammalian species worldwide, including humans.

     Influenza viruses undergo antigenic drift—acquiring frequent mutations in HA and NA, which enables the virions to evade the pre-existing immunity to cause seasonal epidemics/epizootics, and antigenic shift—undergoing gene reassortments causing pandemics. 

    The most important IAV human pandemics: 1918 Spanish flu (H1N1), 1957–1958 Asian flu (H2N2), 1968 Hong Kong flu (H3N2), and 2009 swine-origin H1N1 emerged during the last century [1].

     Structurally, IAV and IBV genomes have eight RNA segments, whereas ICV and IDV have only seven segments. IAV has hemagglutinin (HA), neuraminidase (NA), matrix proteins (M1, M2), and NP (ribonucleoprotein) as structural proteins; 3 subunits of the RNA polymerase complex, polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA); and 3 nonstructural proteins, NS1, NS2/NEP (nuclear export protein), and PB1-F2.

     Studies have shown that NS2 and M1 protein form complexes that can be detected in purified virions and cell lysates of virus-infected cells [2,3]. Hence, NS2 and (probably) NS1 of IAV are not considered as non-structural proteins, as these proteins can be detected in virions [4].

     IBV possesses six structural proteins, HA, NA, NB, M2, M1, NP and NS2; 3 subunits of RNA polymerase complex, PA, PB1, and PB2; and nonstructural protein NS1 [5].

     ICV and IDV have 4 structural proteins, M2, M1, NP, and the hemagglutinin–esterase fusion (HEF) protein that replaces the HA and NA of IAV or IBV; 3 subunits of RNA polymerase complex, P3, PB1, and PB2; and 2 nonstructural proteins, NS1 and NS2.

     IAV has several subtypes based on the HA and NA proteins. Currently, there are 18 HA and 11 NA subtypes, of which H1 to H16 and N1 to N9 have been isolated from birds; the subtypes H17, H18, N10, and N11 have been identified in bats [6,7]. Out of these, only three HA (H1, H2, H3) and two NA (N1, N2) subtypes have been associated with human epidemics and are capable of sustained transmission [8].    KTS. lähdeartikkeli: 

    2019 Jun 17;11(6):561. doi: 10.3390/v11060561

    PMCID: PMC6631717  PMID: 31213032Abstract

    Paradigman muutos(1) märehtivän (ruminantia) nautakarjan A influenssavirusalttiuksista (Bovine A influenza)

    1. 

     Mitä tiedetään nautakarjan influenssoista edellisvuosikymmniltä- Artikkeli vuodelta 

    . 2019 Jun 17;11(6):561. doi: 10.3390/v11060561

    PMCID: PMC6631717  PMID: 31213032Abstract

    It is quite intriguing that bovines were largely unaffected by influenza A, even though most of the domesticated and wild animals/birds at the human–animal interface succumbed to infection over the past few decades. Influenza A occurs on a very infrequent basis in bovine species and hence bovines were not considered to be susceptible hosts for influenza until the emergence of influenza D. This review describes a multifaceted chronological review of literature on influenza in cattle which comprises mainly of the natural infections/outbreaks, experimental studies, and pathological and seroepidemiological aspects of influenza A that have occurred in the past. The review also sheds light on the bovine models used in vitro and in vivo for influenza-related studies over recent years. Despite a few natural cases in the mid-twentieth century and seroprevalence of human, swine, and avian influenza viruses in bovines, the evolution and host adaptation of influenza A virus (IAV) in this species suffered a serious hindrance until the novel influenza D virus (IDV) emerged recently in cattle across the world. Supposedly, certain bovine host factors, particularly some serum components and secretory proteins, were reported to have anti-influenza properties, which could be an attributing factor for the resilient nature of bovines to IAV. Further studies are needed to identify the host-specific factors contributing to the differential pathogenetic mechanisms and disease progression of IAV in bovines compared to other susceptible mammalian hosts.

    Keywords: ruminants, bovine, cattle outbreaks, Influenza A, host restriction, bovine cell cultures, bovine respiratory disease, bronchopneumonia, epizootic cough, seroprevalence, MDBK cells

    Kts. jatkoa 2. Introduction ( ylläolevaan artikkeliin kuuluvaa) 

    torsdag 3 juli 2025

    Sars-1 Covid-19 osoittaa kohonneita ilmenemisiään paikoitellen maapallolla viime viikkoina

     https://data.who.int/dashboards/covid19/summary?n=o

    WHO tiedottaa:

    SARS-CoV-2 reported cases: Last 28 days

    In the 28-day period from 19 May 2025 to 15 June 2025, 87 countries across five WHO regions reported new COVID-19 cases. During this 28-day period, a total of 346,183 new cases were reported, which is an increase compared to the 141,796 new cases reported from 93 countries in the previous 28-day period (Table 2). Overall, 50 countries from Africa, the Americas, Europe, and South-East Asia showed an increase in new cases of over 10%.

     


    Country level details are available in | Cases section

    Table 2.1. Newly reported COVID-19 confirmed cases by WHO regions

    28-days to the date
    WHO Region 18 May 2025 15 Jun 2025
    World 141,796 346,183
    Africa 205 138
    Americas 11,600 11,065
    Eastern Mediterranean No value No value
    Europe 14,070 18,613
    South-East Asia 115,885 316,364
    Western Pacific 36 3

    Table 2.2. Number of countries reported newly COVID-19 confirmed cases by WHO regions

    28-days to the date
    WHO Region 18 May 2025 15 Jun 2025
    World 93 87
    Africa 26 22
    Americas 25 25
    Eastern Mediterranean 0 0
    Europe 36 33
    South-East Asia 4 5
    Western Pacific 2 2

     


    SARS-CoV-2 variant circulation: Last 28 days

    WHO is currently tracking several SARS-CoV-2 variants:


    • Variants of Interest: JN.1
    • Variants Under Monitoring: LP.8.1, NB.1.8.1, XFG, XEC, KP.3.1.1, and KP.3

    The most prevalent variant, LP.8.1, accounted for 26% of all submitted sequences in the week ending on 15 June 2025 which is a decrease from 28% in the week ending on 18 May 2025. NB.1.8.1 accounted for 24% of all submitted sequences in the week ending on 15 June 2025, a slight increase from 23% in the week ending on 18 May 2025. XFG accounted for 19% of all submitted sequences in the week ending on 15 June 2025, a significant increase from 10% in the week ending on 18 May 2025 (Table 3).


    During this reporting period, all other variants showed a decreasing or stable trend. Available evidence suggests that LP.8.1, NB.1.8.1, and XFG do not pose additional public health risks relative to other currently circulating SARS-CoV-2 variants. Due to proportionally low detections (less than 1%) for consecutive weeks, LB.1 has been deescalated from being a VUM.


    At the regional level, in the week ending on 15 June 2025 compared to the week ending on 18 May 2025, LP.8.1 declined in the European Region, the Western Pacific Region, and the Americas, which were the regions with sufficient data. NB.1.8.1 declined in the Americas but increased in the European Region and the Western Pacific Region. XFG increased in all regions with sufficient data. Additionally KP.3.1.1 increased in the Western Pacific Region and JN.1 increased in the Americas.

     


    Country level details are available in | Circulation section

    Information on WHO variant monitoring is available in | Variant section

    Table 3. Weekly prevalence of SARS-CoV-2 VOIs and VUMs

    Variant Variant type 18 May 2025 25 May 2025 1 Jun 2025 8 Jun 2025 15 Jun 2025
    JN.1 VOI 12.4 14.6 15 12.1 12.4
    KP.3
    VUM 1.51 2.02 1.4 1.22 1.32
    KP.3.1.1
    VUM 5.11 4.87 4.67 3.39 3.7
    LP.8.1
    VUM 28.1 27.2 21.9 24.9 25.7
    NB.1.8.1
    VUM 23.5 23.7 23.9 26.1 23.8
    XEC
    VUM 11.7 7.94 6.61 5.69 6.08
    XFG
    VUM 10.2 13.2 19.4 20.3 19.1

    Footnote: Variants presented in this table include the respective descendant lineages, except those individually specified elsewhere in the table.