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#Pathogenicity and #transmissibility of bovine-derived HPAI #H5N1 B3.13 virus in #pigs

Abstract Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle , the virus has continued to spread, reaching at least 17 states and at least 950 dairy herds in the United States. Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important reservoir in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated. Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus . Infectious virus was mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points, suggesting limited replication of the bovine-derived HPAI H5N1 B3.13 virus in pigs. In one animal, we detected the emergence of a mutation in hemagglutinin (HA) previously associated with increased affinity ...

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

  On the 19th of May, an official veterinary doctor was called to the farm due to suspected influenza, as there was an increase in mortality within the animals. On the same day, samples were taken and sent to the Bulgarian National Laboratory for Avian Influenza, where, on the 20th of May, it was confirmed that the farm was affected by a highly pathogenic avian influenza virus. Source: WOAH,  https://wahis.woah.org/#/in-review/6490 ____

A protective and broadly binding #antibody class engages the #influenza virus #hemagglutinin head at its stem interface

ABSTRACT Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic . However, antibodies directed to conserved sites can confer broad protection. Here, we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein. Prototype antibody S8V1-157 binds at the normally occluded interface between the HA head and stem. Antibodies to this HA head–stem interface epitope are non-neutralizing in vitro but protect against lethal influenza infection in mice. These antibodies bind to most influenza A subtypes and seasonal human variants, and are present at low frequencies in the memory B cell populations of multiple human donors. Vaccines designed to elicit these antibodies might contribute to “universal” influenza immunity. IMPORTANCE Antibodies to the influenza virus hemagglutinin (HA) protein confer the strongest p...

Characterization of emerging #H3N3 avian #influenza viruses in #poultry in #China

Abstract Avian influenza viruses continue to challenge poultry and human health ; therefore, careful surveillance and evaluation of emerging viruses are important for animal disease control and human influenza pandemic preparedness . In this study, we detected a series of H3N3 subtype avian influenza viruses in chickens , pigeons, and ducks during our routine surveillance and diagnosis between September 2022 and May 2023. We performed extensive analyses to fully understand the origins of these viruses and their risk to animals and humans. We found that the viruses were complex reassortants ; the viruses from chickens and pigeons carry genes mainly derived from H3N8 viruses and H10N3 viruses , whereas the two duck viruses were reassortants of duck and wild bird viruses. The chicken and pigeon , but not duck, viruses replicated in multiple organs of chickens and were shed for up to 13 days, but none caused disease or death. Six of the viruses tested all bound to both avian- and human-typ...

Investigating Factors Driving Shifts in Subtype #Dominance within #H5Nx Clade 2.3.4.4b High-Pathogenicity Avian #Influenza viruses

Abstract H5Nx clade 2.3.4.4b high-pathogenicity avian influenza viruses (HPAIVs) have decimated wild bird and poultry populations globally since the autumn of 2020. In the United Kingdom (UK) and in continental Europe , the H5N8 subtype predominated during the first epizootic wave of 2020/21 , with few detections of H5N1. However, during the second (2021/22) and third (2022/23) epizootic waves, H5N1 was the dominant subtype. The rapid shift in dominance from H5N8 to H5N1 was likely driven by a combination of virological, immunological, and/or host-related factors. In this study, we compared viral fitness and immunological responses in ducks , a key reservoir species, using dominant genotypes of H5N1 (genotype AB) and H5N8 (genotype A) from the second wave. While viral shedding dynamics were similar for both viruses, H5N8 was more pathogenic . Antigenic analysis of post-infection duck sera revealed that the haemagglutinin (HA) protein was antigenically similar across clade 2.3.4.4b H5 H...

Long-Term Clinical #Outcomes of #Adults Hospitalized for #COVID19 #Pneumonia

Abstract We conducted a multicenter, observational, 12-month follow-up study to identify the extended health burden of severe COVID-19 pneumonia by characterizing long-term sequelae of acute infection in participants previously enrolled in clinical trials for severe COVID-19 pneumonia requiring hospitalization. Overall, 134 (77.5%) of 173 participants completed the study. At 12 months, 51 (29.5%) participants reported cough , 60 (34.7%) reported dyspnea , 56 (32.4%) had residual lung texture abnormalities on high-resolution computed tomography scans, 26 (15.0%) had impaired forced vital capacity , 52 (30.1%) had cognitive impairment , and 77 (44.5%) reported fatigue . Disease severity during acute infection and age were associated with persistent lung abnormalities ; history of hypertension was associated with higher prevalence of fatigue and more frequent dyspnea and cough; and age and obesity were associated with long-term cognitive impairment . Our findings underscore the long-term ...

Progressive #Adaptation of Subtype #H6N1 Avian #Influenza Virus in #Taiwan Enhances #Mammalian #Infectivity, Pathogenicity, and #Transmissibility

Abstract The interspecies transmission of avian influenza viruses remains a significant public health concern. H6 viruses have gained attention following the first human infection by a chicken-origin H6N1 virus (A/Taiwan/02/2013, Hu/13), highlighting their zoonotic potential . To understand the evolutionary trajectory and mammalian adaptation of this Taiwan lineage , we compared two avian isolates (A/Chicken/Taiwan/CF19/2009, Ck/09; A/Chicken/Taiwan/2267/2012, Ck/12) and Hu/13 in vitro and in vivo. Hu/13 exhibited enhanced replication in MDCK cells , producing larger plaques and higher viral titers than Ck/09 and Ck/12. In BALB/c mice , Hu/13 demonstrated the highest pathogenicity and mortality , followed by Ck/12, while Ck/09 induced minimal morbidity. Hu/13 and Ck/12 replicated efficiently in respiratory tissues , eliciting robust cytokine responses and severe pulmonary lesions . In ferrets , Hu/13 showed relatively efficient transmission , infecting all direct physical-contact and t...

#Phylogenetic Analysis and Spread of HPAI #H5N1 in Middle Eastern Countries Based on #Hemagglutinin and #Neuraminidase Gene Sequences

Abstract Highly pathogenic avian influenza (HPAI) A/H5N1 viruses threaten animal and human health worldwide . The first documented cases in the Middle East were reported in 2005 ; however, despite extensive phylogenetic studies , there is limited information on the transmission dynamics of the virus within this region. We analyzed HA and NA gene sequences from various hosts to address this gap and to understand the virus’s spread and evolution in the Middle East. We hypothesized that H5N1 transmission exhibits host-specific or geographically influenced clade structures in this region . This study traced transmission pathways of HPAI A/H5N1 through a phylogenetic and amino acid sequence analysis of HA and NA gene segments from isolates across different hosts in Middle Eastern countries, using the MUSCLE algorithm for alignments and MEGA11 software for phylogenetic analysis. Sequences were selected from NCBI’s virus database based on geographic and host diversity, including those from bi...

Avian #Influenza Virus #Infections in #Felines: A Systematic Review of Two Decades of Literature

Abstract As an avian influenza virus (AIV) panzootic is underway , the threat of a human pandemic is emerging . Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family , the Felidae , is of particular concern. Domestic cats are susceptible to AIV infection and provide a potential pathway for zoonotic spillover to humans. Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of AIV infections in felines reported from 2004 to 2024. We identified 607 AIV infections in felines , including 302 associated deaths , comprising 18 countries and 12 felid species . We observed a drastic flux in the number of AIV infections among domestic cats in 2023 and 2024, commensurate with the emergence of H5N1 clade 2.3.4.4b. We estimate that this phenomenon is underreported in the scientific literature and argue that increased surveillance among domestic cats is urgently needed. Sou...

Endemic #coronavirus #infection is associated with #SARS-CoV-2 Fc receptor-binding #antibodies

ABSTRACT Recent documented infection with an endemic coronavirus (eCoV) is associated with less severe coronavirus disease 2019 (COVID-19), yet the immune mechanism behind this protection has not been fully explored. We measured both antibody and T-cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in SARS-CoV-2- naïve individuals , classified into two groups: those with or without presumed recent eCoV infections . There was no difference in neutralizing antibodies and T-cell responses against SARS-CoV-2 antigens between the two groups. SARS-CoV-2-naïve individuals with recent presumed eCoV infection, however, had higher and significantly correlated levels of Fc receptor (FcR)-binding antibodies against eCoV spikes (S) and SARS-CoV-2 S2. Recent eCoV infection boosts cross-reactive antibodies that can mediate Fc effector functions, and this may play a role in the observed heterotypic immune protection against severe COVID-19. IMPORTANCE With the recent e...

World #Health #Assembly adopts historic #Pandemic #Agreement to make the world more equitable and safer from future pandemics (#WHO)

Agreement’s adoption follows three years of intensive negotiation launched due to gaps and inequities identified in national and global COVID-19 response. Agreement boosts global collaboration to ensure stronger , more equitable response to future pandemics. Next steps include negotiations on Pathogen Access and Benefits Sharing system. Member States of the World Health Organization (WHO) today formally adopted by consensus the world's first Pandemic Agreement. The landmark decision by the 78th World Health Assembly culminates more than three years of intensive negotiations launched by governments in response to the devastating impacts of the COVID-19 pandemic, and driven by the goal of making the world safer from – and more equitable in response to – future pandemics. “The world is safer today thanks to the leadership , collaboration and commitment of our Member States to adopt the historic WHO Pandemic Agreement,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General.  “The Ag...

Circulating vaccine-derived #poliovirus type 2 (#cVDPV2) - #Papua New Guinea (#WHO D.O.N., May 20 '25)

{Summary} Situation at a glance On 9 May 2025, the International Health Regulations (IHR) National Focal Point (NFP) for Papua New Guinea (PNG) notified WHO of the detection of circulating vaccine-derived poliovirus type 2 (cVDPV2) from stool specimens of two healthy children from Morobe province, Papua New Guinea (PNG).  The detection of wild poliovirus (WPV) or vaccine-derived poliovirus (VDPV), including from samples taken from healthy children, is considered a serious public health event .  Given the country's suboptimal routine immunization coverage , especially at the subnational level, the risk of potential spread locally is considered high .  WHO advises all countries —especially those with frequent travel and connections to polio-affected areas—should strengthen acute flaccid paralysis (AFP) and environmental surveillance while maintaining high level of immunization coverage to quickly detect and respond to virus importation and prevent further spread by closing ...

Temperature-dependent #modulation of aberrant #influenza A virus #RNA #synthesis affects innate immune signaling

Abstract Fever during influenza A virus (IAV) infection is triggered by the innate immune response . Various factors contribute to this response, including IAV mini viral RNAs (mvRNA), which trigger RIG-I signaling when their replication and transcription are dysregulated by template loops (t-loop). It is presently not well understood whether the fever response to IAV infection impacts subsequent viral replication and innate immune activation . Here we show that IAV infection at temperatures that simulate fever leads to increased mvRNA synthesis and antiviral signaling . Mathematical modeling and experimental analyses reveal that differential IAV nucleoprotein and RNA polymerase production underlies the increased mvRNA level. Moreover, at the higher infection temperature mvRNAs with dysregulating t-loops contribute most to the innate immune activation. We propose that fever during IAV infection can establish a positive feedback loop in which elevated aberrant RNA synthesis and innate i...

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

  Increased mortality of poultry, clinical signs, commercial holding of pheasants, hens, ducks, geese, peacocks. Source: WOAH,  https://wahis.woah.org/#/in-review/6486 ____

Pharmacodynamic Effect of Different Dosage Regimes of #Oseltamivir in Severe #Influenza Patients Requiring Mechanical #Ventilation: A Multicentre Randomised Controlled Trial

ABSTRACT Background and Objectives This randomised controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in severe influenza patients requiring invasive mechanical ventilation. Methods Forty intubated adult patients with severe influenza A or B from four intensive care units in Hong Kong were enrolled and randomised to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for 10 days. Baseline data were collected, and outcomes were assessed daily using SOFA and Murray scores. Viral RNA was quantified from nasopharyngeal and tracheal aspirates. The primary outcome was the viral clearance rate after 5 days of treatment; secondary outcomes included 28-day and hospital mortality rates, changes in viral load, and serial SOFA and Murray scores. Results Viral clearance rates after 5 days of treatment were low and similar between the double (3/20, 15%) and triple-dose groups (2/20, 10%). No significant di...

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

 The Official Veterinary Services (OVS) received a notification of acute mortality and neurological signs in swans in a zoo. Laboratory analysis identified H5N1 virus clade 2.3.4.4b. OVS is conducting an epidemiological investigation of the event. Source: WOAH,  https://wahis.woah.org/#/in-review/6485 ____

Modeling Effects of Routine #Screening for Accidental #Lab-Acquired #Infections on #Risk of Potential #Pandemic Pathogen #Escape from High-Biosafety Research Facilities

Abstract Accidental lab–acquired infections (LAIs) risk releasing potential pandemic pathogens (PPPs) from BSL–3/4 facilities . We constructed a stochastic network infectious disease model to simulate how the probability of an outbreak of a pathogen resembling wild–type SARS–COV–2, following an initial LAI would be influenced by test–and–isolate interventions over a 100–day horizon . We varied test frequency (0–7 tests/week), peak sensitivity (50–100%), and isolation delay (0–3 days). For each of 192 parameter combinations, we conducted 1,000 simulations and used logistic regression to quantify how each parameter influenced the likelihood of an outbreak of 50 or more infections. Results indicated that even relatively infrequent routine testing significantly reduced the risk of outbreaks under diverse plausible scenarios, with greater reductions achieved at higher test frequencies. Once-weekly testing reduced outbreak risk by 52% under optimistic assumptions (80% sensitivity, 1–day dela...

Baptism of St Zenobius and His Appointment as Bishop (Sandro Botticelli, 1500 - 05)

 Public Domain. Source: WikiArt,  https://www.wikiart.org/en/sandro-botticelli/baptism-of-st-zenobius-and-his-appointment-as-bishop-1505 ____

#Evolution of #Antiviral Drug #Resistance in #SARS-CoV-2

Abstract The COVID-19 pandemic has had a significant impact and continues to alarm the entire world due to the rapid emergence of new variants , even after mass vaccinations . There is still an urgent need for new antivirals or strategies to combat the SARS-CoV-2 infections; however, we have success stories with nirmatrelvir . Drug repurposing and drug discovery may lead to a successful SARS-CoV-2 antiviral; however, rapid drug use may cause unexpected mutations and antiviral drug resistance. Conversely, novel variants of the SARS-CoV-2 can diminish the neutralizing efficacy of vaccines, thereby enhancing viral fitness and increasing the likelihood of drug resistance emergence. Additionally, the disposal of antivirals in wastewater also contributes to drug resistance. Overall, the present review summarizes the strategies and mechanisms involved in the development of drug resistance in SARS-CoV-2. Understanding the mechanism of antiviral resistance is crucial to mitigate the significant...