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#Influenza A Virus #infection is associated with TDP-43 #pathology and neuronal #damage in the #brain

Abstract Viral pandemics such as COVID-19 have demonstrated long-term neurological consequences , including memory impairment and depression , emphasizing the importance of understanding virus-brain interactions [1]. Similar concerns have been raised for Influenza A virus (IAV), which has been implicated in neurodegenerative disorders [2, 3]. In this study, we investigated the neuropathological effects of highly pathogenic avian influenza (HPAI) H5N1 and H5N8 strains in a mouse model . Although viral RNA was detected in the brain post-infection, no viral proteins were found, suggesting limited or transient brain replication . Despite this, infected brains showed significant neuronal damage , including axonal loss and nuclear condensation , as evidenced by immunofluorescence and Nissl staining. We also observed pathological changes in TDP-43, including conformational alterations and increased phosphorylation, which required antigen retrieval for detection, features reminiscent of those ...

A 15-year study of #neuraminidase #mutations and the increasing of S247N mutation in #Spain

Highlights •  In a landscape of a very narrow arsenal of influenza antivirals, resistance mutations are a significant threat. •  Resistance mutations were present in 0.5-5% in A and B influenza viruses during the last 15 years. •  However, S247N resistance mutation in the NA gene sharply increased during 2023-2024 season. •  While this mutation does not confer strong resistance by itself, their fixation could increase the risk of resistance in the future if other resistance mutations appears or get fixed together with it. Abstract The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations , especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain . To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences , and analyzed the resistance m...

A single-dose #intranasal #immunization with a novel #bat #influenza A virus-vectored #MERS #vaccine provides effective protection against lethal MERS-CoV challenge

ABSTRACT The threat to global health security posed by Middle East respiratory syndrome coronavirus (MERS-CoV) and emerging MERS-like coronaviruses highlights the need to develop safe and efficient vaccines. Viral vector vaccines have been shown to be effective and are widely used to prevent various viral diseases because they mimic natural infection and induce a more comprehensive immune response. Herein, we developed a novel bat influenza A virus-based vaccine vector by replacing the open reading frame of either bat influenza hemagglutinin or neuraminidase with that of the hemagglutinin-esterase-fusion gene from influenza D virus , which can infect multiple species, including humans and camels . We then generated a temperature-sensitive, cold-adapted, and attenuated MERS vaccine candidate expressing the clade A MERS-CoV spike S1, referred to as Len_S1, using the developed bat influenza vector and demonstrated its safety and immunogenicity. A single-dose intranasal immunization with L...

#Genetic #resilience or #resistance in #poultry against avian #influenza virus: mirage or reality?

ABSTRACT The unprecedented global spread of the highly pathogenic avian influenza (HPAI) virus in wild birds, poultry, and mammalian species has challenged our control efforts. Alternative approaches to limit avian influenza viruses (AIV) include the development of resilient or resistant chickens . Genetically resilient birds may become infected but can overcome disease, whereas resistant birds prevent virus attachment or entry and do not become infected. The most intensively studied host gene is myxovirus-resistance (Mx), which is expressed via the interferon pathway . Both sensitive and resistant chicken Mx genotypes have been described, but this only provides limited resilience . Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been demonstrated as a host cofactor for AIV replication via interaction with the polymerase. Small nucleotide changes within this gene have demonstrated some promise for the establishment of disease resilience. Certain MHC-defined genetic chicke...

#Cambodia records 11th #human case of #H5N1 #birdflu in 2025

  PHNOM PENH, July 1 (Xinhua) -- A 36-year-old woman from northwest Cambodia's Siem Reap province has been confirmed for H5N1 human avian influenza, raising the number of the cases to 11 so far this year , the Ministry of Health said in a statement on Tuesday. "A laboratory result from the Pasteur Institute in Cambodia showed on June 30 that the woman was positive for H5N1 virus," the statement said. "The patient has the symptoms of fever, cough, and dyspnea , and she is currently being rescued by a team of doctors." The victim lives in Doun Keo village of Puok district. There were sick and dead chickens at the patient's home. She had been in contact with those dead chickens and took them to bury. Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victim in order to prevent an outbreak in the community. Tamiflu (oseltamivir), an antiviral drug to prevent the bird f...

#Cambodia reported four additional #human cases of #infection with #influenza A #H5N1 virus during week 26/2025 (HK CPH, July 1 '25)

  {Excerpt} [Date of report - Country - Province / Region - District - City - Sex - Age - Condition at time of reporting  - Subtype of virus]  1) 24/06/2025 - Cambodia - Siem Reap province  - F - 41 - Critical  - H5N1  2) 29/06/2025 - Cambodia -  Siem Reap province  - F - 46 - Stable - H5N1  3) 29/06/2025 - Cambodia -  Siem Reap province  - M - 16 - Stable - H5N1  4) 30/06/2025 - Cambodia -  Takeo province - M - 19 months  - Deceased - H5N1  (...) Source: Centre for Health Protection, Hong Kong PRC SAR,  https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk26.pdf ____

#Monkeypox virus spreads from #cell-to-cell and leads to #neuronal #death in human neural #organoids

Abstract In 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. Here, we analyze the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate . We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons . The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories . Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus , suggesting viral cell-to-cell spread . Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission . We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative diso...

The Lookout – "All's Well", Winslow Homer (1896)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/winslow-homer/the-lookout-alls-well-1896 ____

#H5N1 Avian #Influenza: A Narrative #Review of Scientific Advances and #Global #Policy Challenges

Abstract The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission . Recent scientific advances have included the development of next-generation vaccine platforms , promising antiviral compounds , and more sensitive diagnostic tools , alongside strengthened surveillance systems in both animals and humans. However, persistent structural challenges hinder global readiness. Vaccine production is heavily concentrated in high-income countries, limiting equitable access during potential pandemics. Economic and logistical barriers complicate the implementation of control strategies such as vaccination, culling, and compensation schemes. Gaps in international coordination , public communication, and standardization of protocols further exacerbate vulnerabilities. Although sustained human-to-human transmission has not been documented, the severity of confirmed infections and the rapid global s...

{A family cluster of cases:} #Mother, #son contract #H5N1 #birdflu in #Cambodia

  PHNOM PENH, June 29 (Xinhua) -- A 46-year-old Cambodian mother and her 16-year-old son have been confirmed positive for H5N1 human avian influenza, bringing the total number of cases to 10 so far this year, the Ministry of Health said in a statement on Sunday. Both victims live in Lbeuk village of Puok district in northwest Siem Reap province. "According to queries, there were sick and dead poultry at the patients' home and their neighbors' homes as well as in the village, and the patients had been in contact with sick and dead chickens and cooked them for food," it added. Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victims in order to prevent an outbreak in the community. Tamiflu (oseltamivir), an antiviral drug to prevent the bird flu from spreading, was also given out to people who had direct contact with the patients, the statement said. So far this year, the ki...

Detection of clade 2.3.4.4b #H5N1 high pathogenicity avian #influenza virus in a #sheep in #UK, 2025

Abstract Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) continues to pose a significant global threat , affecting wild and domestic avian populations, and mammalian species . In early 2024, H5N1 HPAIV was detected in dairy cattle in the United States of America, where it has continued to circulate, with sporadic detections also reported in other ruminant species . The detection of high viral loads in milk from infected cattle, has resulted in several human infections , underscoring the zoonotic potential of these viruses. In response, several countries have intensified surveillance in non-avian species to evaluate the potential for undetected viral circulation in captive mammals. In Great Britain, bulk milk tank testing of cattle and targeted surveillance of captive mammalian species on an infected premises is undertaken in accordance with the outcome of a rapid risk assessment undertaken to determine the epidemiological links between the poultry and captive mamma...

Phylogenetic and #Mutation #Analysis of #Hemagglutinin Gene from Highly Pathogenic Avian #Influenza Virus #H5 Clade 2.3.4.4b in South #America

Abstract The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America . The introduction of the virus into South America was reported for the first time in Colombia in October 2022, followed by outbreaks in other South American countries affecting poultry, wild birds, mammals , and humans . In this study, a phylogenetic and mutation analysis of the hemagglutinin (HA) gene of HPAIV H5N1 2.3.4.4b viruses isolated in South America was performed to analyze its evolution and its transmission and zoonotic potential . The analysis shows an increase in the viral effective population size between April and June 2022, which was followed by multiple outbreaks of HPAIV H5N1 clade 2.3.4.4b in South America . Moreover, the virus variants evolved from a recent common ancestor estimated to have existed in June 2017. The mean rate o...

History of Mass Transportation: The FS Aln 442 Diesel Multiple-Unit

Di Giorgio Stagni - http://www.stagniweb.it/foto6.asp?File=tee448&righe=1&inizio=45&InizioI=1&RigheI=100&Col=5 , CC BY-SA 3.0,  https://commons.wikimedia.org/w/index.php?curid=96379237 Source: Wikipedia,  https://it.wikipedia.org/wiki/Automotrici_FS_ALn_442-448 ____

#Coronavirus Disease Research #References (by AMEDEO, June 28 '25)

  Antiviral Res HUSSAIN S, Meijer A, Govorkova EA, Dapat C, et al Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. Antiviral Res. 2025 Jun 24:106217. doi: 10.1016/j.antiviral.2025.106217. PubMed           Abstract available Clin Infect Dis HARUN MGD, Sumon SA, Anwar MMU, Mohona TM, et al Infection Prevention and Control Knowledge, Attitudes, and Practices of Healthcare Workers in Tertiary Care Hospitals in Bangladesh During Coronavirus Disease 2019: A Multicenter Cross-sectional Survey. Clin Infect Dis. 2025 Jun 25:ciaf246. doi: 10.1093. PubMed           Abstract available DUONG KS, Henry SS, Duong TQ SARS-CoV-2 infection increases long-term risk of pneumonia in an urban population: an observational cohort study up to 46 months post-infection. Clin Infect Dis. 2025 Jun 25:ciaf345. doi: 10.1093. PubMe...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, June 28 '25)

  Antimicrob Agents Chemother MENG X, Zhang C, Wang X, Shi J, et al A branched peptide targets virus and host to block influenza virus and rhinovirus entry. Antimicrob Agents Chemother. 2025 Jun 25:e0002425. doi: 10.1128/aac.00024. PubMed           Abstract available Antiviral Res HUSSAIN S, Meijer A, Govorkova EA, Dapat C, et al Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. Antiviral Res. 2025 Jun 24:106217. doi: 10.1016/j.antiviral.2025.106217. PubMed           Abstract available Biochemistry PANKRATOVA Y, Hong M Side Chain Structures of the Proton-Selective Histidine and Gating Tryptophan in Influenza BM2 Reveal Both Conservation and Variation of the Proton Conduction Mechanism. Biochemistry. 2025 Jun 24. doi: 10.1021/acs.biochem.5c00242. PubMed          ...

Highly Pathogenic Avian #Influenza Virus A #H5N1 subclade 2.3.4.4 b isolated from a European grey #seal (Halichoerus grypus) is highly virulent in #ferrets

  Abstract Highly pathogenic avian influenza A viruses subtype H5N1 (HPAIV H5N1), subclade 2.3.4.4b infect multiple avian and mammalian species , posing a potential pandemic risk . Here we describe the outcomes of infection of ferrets with a HPAIV H5N1 virus, isolated from a European grey seal in 2023, compared with an older HPAIV H5N1 (A/Indonesia/05/2005). Overall, infection of ferrets with A/grey seal/Netherlands/302603/2023 caused more rapid mortality than infection of ferrets with A/Indonesia/05/2005. Animals developed severe pneumonia and irreversible hypothermia , associated with high levels of virus replication and histopathological changes in the respiratory tract and peripheral organs. As animal models for severe avian influenza virus infections in humans play a key role in the development of intervention strategies against these infections, these findings highlight the importance of using updated ferret models based on circulating virus strains. Source: Journal of Infect...

Seventh #Update on #Developments in #Iran (#War) (#IAEA, June 27 '25)

  Radiation levels in the Gulf region remain normal following the 12-day conflict that severely damaged several nuclear facilities in Iran , Director General Rafael Mariano Grossi of the International Atomic Energy Agency (IAEA) said today. Citing regional data reported regularly to the IAEA through the International Radiation Monitoring System (IRMIS), Director General Grossi noted that this 48-nation network would have detected an important radioactive release from any damaged nuclear power reactor. “From a nuclear safety perspective, Iran’s Bushehr Nuclear Power Plant and the Tehran Research Reactor represented our main concern as any strike affecting those facilities – including their off-site power lines – could have caused a radiological accident with potential consequences in Iran as well as beyond its borders in the case of the Bushehr plant. It did not happen, and the worst nuclear safety scenario was thereby avoided,” Director General Grossi said. Stressing again that nuc...

Production and Immune Response Against #Pandemic #Influenza Candidate #Vaccines as Preparedness Against the Circulating #H5N1 Influenza Viruses

Abstract Background/Objectives : H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern.  Methods :  The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity.  Results :  Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale ...

#Mpox, Multi-country external #situation #report no. 54 published 27 June (#WHO)

{Summary) KEY FIGURES   {Area - Number of reported confirmed cases - Number of deaths among confirmed cases - Number of reporting countries} -- Global (1 Jan – 31 May 2025)* - 24 672 - 82 - 75  Key countries (01 Jan – 22 June 2025) - Democratic Republic of the Congo - 12 208 - 22 - ... - Uganda - 5636 - 31  - ... - Sierra Leone - 4294 - 28 - ... - Burundi - 1079 - 0 - ... {*} Most recent global surveillance data available. Highlights • In May 2025, a total of 6823 confirmed mpox cases and 16 deaths (Case Fatality Ratio: 0.2%) were reported from 49 countries across all WHO regions. • The majority of mpox cases continue to be reported from the WHO African Region , with 18 countries currently experiencing active ongoing transmission. • Since the last report, Ethiopia and Italy have reported their first cases of mpox due to clade Ib monkeypox virus (MPXV). In addition, North Macedonia, the Republic of the Congo, and Togo have reported their first cases of mpox clade IIb MPXV ...

#Evolution of #antibody cross-reactivity to #influenza #H5N1 #neuraminidase from an N2-specific germline

Abstract The ongoing spread of highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus in animals and occasional spillover to humans have raised concerns about a potential H5N1 pandemic. Although recent studies have shown that pre-existing human antibodies can recognize H5N1 neuraminidase , there is a lack of molecular understanding of how this cross-reactivity develops. Using a phage display antibody library derived from 245 healthy donors , this study isolates an antibody, known as HB420 , that cross-reacts with the neuraminidases of human H3N2 and avian H5N1 clade 2.3.4.4b viruses and confers protection in vivo. Cryo-EM analysis shows that HB420 targets the neuraminidase active site by mimicking sialic acid binding through a single Asp residue. Additionally, the inferred germline of HB420 is N2-specific but acquires cross-reactivity to H5N1 neuraminidase through somatic hypermutations . Overall, our findings provide insights into how neuraminidase antibody evolves breadth, which...