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Synergistic effects of PA (S184N) and #PB2 (E627K) #mutations on the increased pathogenicity of #H3N2 canine #influenza virus #infections in mice and #dogs

ABSTRACT As companion animals, dogs are susceptible to various subtypes of influenza A virus (IAV), with the H3N2 and H3N8 subtypes of canine influenza virus (CIV) stably circulating among canines . Compared to the H3N8 CIV, the H3N2 CIV is more widely prevalent in canine populations and demonstrates increased adaptability to mammals , potentially facilitating cross-species transmission . Therefore, a comprehensive elucidation of the mechanisms underlying H3N2 CIV adaptation to mammals is imperative. In this study, we serially passaged the GD14-WT strain in murine lungs , successfully establishing a lethal H3N2 CIV infection model . From this model, we isolated the lethal strain GD14-MA and identified the key lethal mutations PA(S184N) and PB2(E627K). Moreover, the GD14-ma[PA(S184N)+PB2(E627K)] strain exhibited markedly enhanced pathogenicity in dogs . Viral titers in lung tissues from infected dogs and mice showed that GD14-ma[PA(S184N)+PB2(E627K)] does not increase its pathogenicity ...

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {as of April 4 '25}

  {Excerpt} Time Period: March 23, 2025 - March 29, 2025 -- H5 Detection :  9 sites ( 2.2% ) -- No Detection :  400 sites ( 97.8% ) -- No samples in last week :  228 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

#Nirmatrelvir–ritonavir versus placebo–ritonavir in individuals with #longCOVID in the #USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial

Summary Background The substantial burden of post-COVID-19 condition (also known as long COVID) underscores the need for effective pharmacological interventions. Given that viral persistence has been hypothesised as a potential cause of long COVID, antiviral therapy might offer a promising approach to alleviating long COVID symptoms. We therefore investigated the efficacy, safety, and tolerability of nirmatrelvir–ritonavir for treating long COVID. Methods In this phase 2, decentralised, double-blind, randomised controlled trial , adults (aged ≥18 years) from the 48 states across the contiguous USA, with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks, were eligible for inclusion. Key exclusion criteria were use of nirmatrelvir–ritonavir within the previous 2 months, CYP3A4-dependent medications, or strong CYP3A4 inducers; acute medical illness such as SARS-CoV-2 infection within the past ...

#Influenza #H1N1pdm09 Virus with Reduced Susceptibility to #Baloxavir, #Japan, 2024

Abstract Influenza A(H1N1)pdm09 virus carrying an I38N substitution was detected in an untreated teenager in Japan . The I38N mutant virus exhibited reduced susceptibility to baloxavir but remained susceptible to neuraminidase inhibitors and showed reduced growth capability . Monitoring antiviral drug susceptibility of influenza viruses is necessary to aid public health planning and clinical recommendations. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/5/24-1123_article ____

#Outbreak of #Marburg Virus Disease, Equatorial Guinea, 2023

Abstract In February 2023, the government of Equatorial Guinea declared an outbreak of Marburg virus disease . We describe the response structure and epidemiologic characteristics , including case-patient demographics, clinical manifestations, risk factors , and the serial interval and timing of symptom onset, treatment seeking, and recovery or death . We identified 16 laboratory-confirmed and 23 probable cases of Marburg virus disease in 5 districts and noted several unlinked chains of transmission and a case-fatality ratio of 90% (35/39 cases). Transmission was concentrated in family clusters and healthcare settings . The median serial interval was 18.5 days ; most transmission occurred during late-stage disease . Rapid isolation of symptomatic case-patients is critical in preventing transmission and improving patient outcomes; community engagement and surveillance strengthening should be prioritized in emerging outbreaks. Further analysis of this outbreak and a One Health surveillan...

#Genomic #signatures and #host #adaptation of #H5N1 clade 2.3.4.4b: A call for global #surveillance and multi-target antiviral strategies

Highlights •  Phylogenetic analysis of genotype B3.13 and D1.1 across the species. •  Mutations on the receptor binding sites related to receptor preferring. •  Host adaptability differences between B3.13 and D1.1. •  Antivirals resistance mutations emergence of genotype B3.13 and D1.1. Abstract The recent report of the first fatality associated with infection by influenza virus H5N1 clade 2.3.4.4b, identified as genotype D1.1, which is distinct from the B3.13 genotype, has sparked fears of a potential human pandemic . However, the genetic relationships between B3.13 and D1.1, as well as their origins, host adaptability, and antiviral resistance, remain poorly understood . Here we conducted a comprehensive phylogenetic and comparative analysis of H5N1 clade 2.3.4.4b across multiple species , in order to identify the molecular characteristics and frequency of resistance mutations in these two genotypes, elucidate their evolutionary trajectories , and assess their impl...

A #Wildlife #Health #Outbreak #Response Table-top Exercise for #Pandemic Preparedness #Planning

Abstract Zoonotic diseases have received significantly more attention over the last few decades , emerging with increasing frequency and causing the majority of notable disease outbreaks in this century, including the COVID-19 pandemic . As human activities and shifting climate patterns induce changes in the environment that alter habitat and range of reservoir species , the potential for human and animal interactions will increase and enhance the opportunity for spillover . Thus, any emergency response preparedness planning must take into account the function and coordination of agencies across the sectors of human, animal and environmental health. Within the Commonwealth of Pennsylvania a table-top exercise was performed to evaluate a multi-agency response during a hypothetical zoonotic disease investigation. The exercise was evaluated by the participants to gain feedback on the overall process and lessons learned. Here, we describe the tabletop exercise scenario and the insights gai...

#NASA #Update on the #Size Estimate and #Lunar #Impact Probability of #Asteroid 2024 #YR4

Since near-Earth asteroid 2024 YR4 was first discovered in December 2024 , NASA and the worldwide planetary defense community have continued to observe the asteroid, which was ruled out as a significant impact risk to Earth . New infrared observations from NASA’s James Webb Space Telescope have decreased the uncertainty of the asteroid’s size and 2024 YR4 is now estimated to be 174-220 feet (53-67 meters), about the size of a 10-story building. The previous size estimate of 131-295 feet (40-90 meters) was derived from visible light measurements from ground-based telescopes.   (...) Experts at NASA’s Center for Near Earth Object Studies at the agency’s Jet Propulsion Laboratory have updated 2024 YR4’s chance of impacting the Moon on Dec. 22, 2032 from 1.7% as of late February to 3.8% based on the Webb data and observations from ground-based telescopes. There is still a 96.2% chance that the asteroid will miss the Moon. In the small chance that the asteroid were to impact, it would n...

#India, Andhra Pradesh reports first #human #death owing to #H5N1 virus

{Excerpt} (...) Samples of a two-year-old girl from Palnadu district’s Narasaraopeta , who died of multi-organ failure at AIIMS-Mangalagiri on March 16, tested positive for H5N1 virus. The confirmation from National Institute of Virology (NIV-Pune) came on March 31. (...) Source: The Hindu,  https://www.thehindu.com/news/national/andhra-pradesh/ap-reports-first-human-death-owing-to-h5n1-virus/article69403347.ece ____

#Clinical presentation of #Oropouche virus #infection: A systematic review and meta-analysis

Abstract Background The recent surge in incidence and geographic spread of OROV infections poses an escalating threat to global public health. However, studies exploring the clinical signs of OROV infection remains exceedingly limited. Methods We searched for OROV studies published until June 17, 2024, in several electronic databases including MEDLINE, EMBASE, SCOPUS, and the Cochrane Library. Results In total, 15 studies involving 806 patients with OROV infection were eligible for inclusion. General symptoms with fever and headache were the most common. Gastrointestinal disturbances like nausea/vomiting, anorexia , and odynophagia were also prevalent, along with ocular symptoms , mainly retro-orbital pain, photophobia, and redness . Respiratory symptoms , such as cough, sore throat and nasal congestion, are present, and skin-related issues like rash, pruritus, and pallor were also identified. Conclusion Overall, this study provides a foundational understanding of OROV’s clinical manif...

Rates of #infection with other #pathogens after a positive #COVID19 test versus a negative test in #US #veterans (November, 2021, to December, 2023): a retrospective cohort study

Summary Background SARS-CoV-2 infection leads to post-acute sequelae that can affect nearly every organ system , including the immune system . However, whether an infection with SARS-CoV-2 is associated with increased risk of future infections with other pathogens is not yet fully characterised. In this study, we aimed to test the association between a positive test for COVID-19, compared with a negative test, and rates of future infections with other pathogens. Methods We used the US Department of Veterans Affairs health-care databases to build a spatiotemporally aligned cohort of 231 899 people with a positive COVID-19 test and 605 014 with a negative COVID-19 test (test-negative control group) between Nov 1, 2021, and Dec 31, 2023. We first did a discovery approach to map the associations between those with a positive COVID-19 test versus a negative test and laboratory-based outcomes of infectious illnesses. We then compared rates of a prespecified set of infectious disease outcomes...

Dairy #cattle #herds mount a characteristic #antibody response to highly pathogenic #H5N1 avian #influenza viruses

Abstract An unprecedented outbreak of a highly pathogenic avian influenza virus, H5 clade 2.3.4.4b, was reported in United States dairy cattle during the spring of 2024. It has now spread to hundreds of herds across multiple states. In humans, antibodies to the hemagglutinin (HA) protein confer the strongest protection against infection. Human herd immunity limits viral spread but also drives the emergence of antigenic variants that escape dominant antibody responses. We used store-bought milk to profile the collective H5N1 antibody response of dairy cattle herds . We detected HA binding antibodies in specific samples from states with recent/ongoing outbreaks. These antibodies present in milk neutralized replicating virus expressing dairy cattle HA and neuraminidase (NA). Despite originating from independent vendors, dairies/plants, geographic regions, and time, antibodies present in these samples are remarkably similar in activity and HA binding specificity. The dominant antibody resp...

Highly pathogenic avian #influenza #management in high-density #poultry #farming areas

Abstract The continuous spread of highly pathogenic avian influenza H5 viruses poses significant challenges, particularly in regions with high poultry farm densities where conventional control measures are less effective. Using phylogeographic and phylodynamic tools , we analysed virus spread in Southwestern France in 2020-21, a region with recurrent outbreaks. Following a single introduction, the virus spread regionally, mostly affecting duck farms , peaking in mid-December with a velocity of 27.8 km/week and an effective reproduction number between farms (Re) of 3.8, suggesting the virus can spread beyond current control radii. Transmission declined after late December following preventive culling. Farm infectiousness was estimated around 9 days. Duck farm density was the main driver of virus spread and we identified farm density and proximity thresholds required to maintain effective control (Re < 1). These findings offer actionable guidance to support regional biosecurity and to...

Intranasal #influenza virus-vectored #vaccine offers protection against clade 2.3.4.4b #H5N1 #infection in small animal #models

Abstract The highly pathogenic avian influenza (HPAI) H5N1 virus has been endemic in aquatic birds since 1997, causing outbreaks in domestic poultry and occasional human infections worldwide. Recently, the cross-species transmission of a new reassortant variant from clade 2.3.4.4b of H5N1 to cattle in the US has heightened concerns regarding the expansion of host range and potential human infection . As eradicating the H5N1 virus from its reservoir is impossible, it is essential to prepare for a potential pandemic caused by an H5N1 derivative. Utilizing a deleted-NS1 live attenuated influenza viral vector vaccine system (DelNS1 LAIV), a system we have previously used in the development of a COVID-19 vaccine, we have rapidly developed an intranasal vaccine for cattle H5N1 and related clade 2.3.4.4b strains, based on publicly available sequences. Our research demonstrates that a single intranasal immunization can provide effective protection against lethal challenges from HPAI cattle or ...

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

On 31 March 2025 a clinical suspicion was reported to the Danish Veterinary and Food Administration. The affected poultry holding consists of 24 hens. On 1 April 2025 highly pathogenic avian influenza subtype H5N1 was confirmed by the national reference laboratory. A 3 km protection zone and a 10 km surveillance zone has been established. The culling was completed on 1 April 2025. Carcasses will be disposed of by rendering. Source: WOAH,  https://wahis.woah.org/#/in-review/6392 ____

#PA and #PAX: two key #proteins from segment 3 of the #influenza viruses

Abstract In recent years, the influenza viruses have posed an increasingly severe threat to public health . It is essential to analyze the virulence and pathogenesis of influenza viruses to prevent and control them, as well as create antiviral drugs . Previous studies have revealed that influenza virus segment 3 codes for not only the PA protein but also a novel protein, PA-X . PA protein is one subunit of the polymerase of influenza viruses and plays a critical role in its life cycle. PA presented endonuclease activity , the transcription and replication of the viral genome , viral virulence , protein degradation , and host immune response by interacting with viral proteins, including PB2, PB1, and host factors, including ANP32A, CHD6, HAX1, hCLE, HDAC6, MCM complex. PA mutations were involved in the viral replication, pathogenicity, and transmission of influenza viruses in poultry, mammals, and humans . PA-X is an open reading frame generated by +1 ribosomal code shift at the N-termi...