Molecular #patterns of #matrix protein 1 (M1): A strong predictor of adaptive #evolution in #H9N2 avian #influenza viruses

Significance

The dominance of the H9N2 subtype of avian influenza virus (AIV) within the influenza A virus family has raised questions regarding the factors influencing its epidemiological dominance. This study concentrates on the role of five major evolutionary patterns of the matrix protein M1 in the replication and transmission of H9N2 AIVs. The findings indicate a strong correlation between the epidemiological dominance of H9N2 AIVs and the specific M1 patterns, particularly M1P5. It highlights the significance of genetic patterns in M1 for understanding the adaptive differences and turnover of epidemiological dominant H9N2 AIVs.

Abstract

The H9N2 subtype of avian influenza virus (AIV) emerges as a significant member of the influenza A virus family. However, the varying degrees of epidemiological dominance among different lineages or clades of H9N2 AIVs have not been fully clarified. The matrix protein M1, a key structural component of the virion, plays a crucial role in maintaining the viral structure and lifecycle. To elucidate the intrinsic relationship between the genetic patterns of M1 and the adaptive dynamics of H9N2 AIVs, this study focused on the five major evolutionary patterns of M1 and conducted in vitro and in vivo investigations from the perspectives of vRNP release after viral uncoating, polymerase activity, mRNA and vRNA levels, the nuclear export of vRNPs, plasma membrane–binding capacity, proliferation capacity, growth competitiveness, and transmission potential. The results revealed a strong correlation between the epidemiological dominance of H9N2 AIVs and the specific patterns of M1, with M1P5 standing out as particularly significant. This finding highlights the pivotal influence of the M1 gene patterns on the replication and transmission dynamics of H9N2 AIVs, thereby offering valuable insights into the mechanisms driving differences in adaptive evolution and shifts in epidemiological dominance within the H9N2 AIV population.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2423983122

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Dynamics of natural #selection preceding #human viral #epidemics and #pandemics.

Abstract

Using a phylogenetic framework to characterize natural selection, we investigate the hypothesis that zoonotic viruses require adaptation prior to zoonosis to sustain human-to-human transmission. Examining the zoonotic emergence of Ebola virus, Marburg virus, influenza A virus, SARS-CoV, and SARS-CoV-2, we find no evidence of a change in the intensity of natural selection immediately prior to a host switch, compared with typical selection within reservoir hosts. We conclude that extensive pre-zoonotic adaptation is not necessary for human-to-human transmission of zoonotic viruses. In contrast, the reemergence of H1N1 influenza A virus in 1977 showed a change in selection, consistent with the hypothesis of passage in a laboratory setting prior to its reintroduction into the human population, purportedly during a vaccine trial. Holistic phylogenetic analysis of selection regimes can be used to detect evolutionary signals of host switching or laboratory passage, providing insight into the circumstances of past and future viral emergence.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.26.640439v1

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Phylogenetic #discordance cannot identify #genomic #reassortment events: a case study with the avian #influenza virus #H5Nx

Abstract

Recombination plays a central role in the evolution of the RNA virus genome, as it allows the exchange of genetic material between different viral lineages. Reassortment is a form of recombination specific to viruses with segmented genomes that involves the exchange of entire segments between lineages. This process has played a significant role in the adaptation and spread of influenza viruses, where novel combinations of genomic segments are produced from divergent lineages (i.e., antigenic shift). In this study, we investigated reassortment events in a representative sample of n = 11, 765 complete genomes of H5Nx influenza A viruses from avian hosts. Using tanglegrams and subtree-prune-regraft (SPR) methods to quantify discordance between segment trees, we found evidence of widespread reassortment among these genomes that is consistent with previous studies. However, we obtained the comparable numbers of reassortment events when applying the same methods to sequence data simulated in the complete absence of any reassortment. This outcome indicates a high false positive rate in identifying reassortment events due to uncertainty in phylogenetic reconstruction. There was also no significant difference between SPR events inferred from real data versus simulated false positives with respect to subtree size, or the distance between prune and regraft points in the reference tree. Although there is no doubt that reassorment has played a significant role in the origin of new pandemic strains of influenza viruses, these results imply that previous reports of extensive reassortment in the avian influenza virus literature should be interpreted with caution.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.24.639875v1

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Elucidating the Characteristics and #Clonal Evolutionary #Trajectory of #Influenza #Neuraminidase Broadly Reactive B Cell

Abstract

Influenza virus neuraminidase (NA) is receiving increasing attention as a target for universal flu vaccines. Several broad NA inhibition monoclonal antibodies (BImAbs) targeting the highly conserved enzymatic pocket have been previously described. However, the molecular characteristics, clonal evolutionary trajectory, and B cell sources of BImAbs remain poorly understood. Here, using NA-mutant probes, we comprehensively profiled the immune signatures of NA-specific memory B cells (MBCs) from a healthy individual with NA cross-inhibition activity. From the NA-specific MBC repertoires, we identified a series of NA BImAbs with molecular features characterized by long HCDR3 regions with an xxxDRxxx motif, which exhibited broad inhibition against diverse influenza NAs. Clonal lineage tracing revealed that these BImAbs followed a clonal evolutionary trajectory encompassing classical MBC (cMBC) and atypical MBC (aMBC). Both cMBC- and aMBC-derived NA BImAbs displayed similar inhibitory activity against the influenza NAs. These findings enhance our understanding of the development of NA BImAbs and provide a foundation for the rational design of NA-based universal flu vaccines.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.23.639775v1

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#USA, #NJ: #H5N1 Highly Pathogenic Avian #Influenza Confirmed in New Jersey Cats {DoH}

TRENTON, NJ - The first feline case of H5 Highly Pathogenic Avian Influenza (HPAI or “bird flu”) in New Jersey has been confirmed in a feral cat from Hunterdon County. 

The case was confirmed by the United States Department of Agriculture (USDA) National Veterinary Services Laboratory, and follows previous national reports of confirmed feline cases in other states.  

The cat developed severe disease, including neurologic signs, and was humanely euthanized. 

Other cats on the same property were also reported ill, and one additional indoor-outdoor cat was subsequently confirmed positive for H5 HPAI. Other tests are still pending, and the investigation is ongoing.

The overall public health risk remains low at this time. While H5 HPAI has been detected in humans in the U.S. – primarily in individuals with close contact with infected poultry or dairy cattle – there have been no human cases reported in New Jersey, and none of the cases across the country are known to have resulted from exposure to an infected cat.

Local health officials are working closely with the New Jersey Department of Health in conducting follow up and symptom monitoring on individuals that have been in contact with these cats. All exposed individuals are currently asymptomatic. 

Residents who have had close, unprotected contact with a cat or other animal infected with H5 HPAI should contact their local health department and monitor themselves for symptoms for 10 days following their last exposure.

“While the risk of H5 infection to the general population remains low at this time, it is important for people to learn more about the situation and take steps to avoid potential infection through exposure to animals, including feral cats,” said New Jersey Health Commissioner Kaitlan Baston, MD, MSc, DFASAM. “We continue to work with state and federal partners to monitor the spread of this virus and provide public information on mitigating the risks.”

Cats are particularly susceptible to H5 HPAI and often experience severe disease and high mortality when infected. Potential exposure sources of H5 HPAI for cats include consuming raw (unpasteurized) milk or raw/undercooked meat contaminated with the virus, infected birds or other animals and their environments, or exposure to contaminated clothing or items (fomites) worn or used on affected premises.

The cats tied to this incident in Hunterdon County had no known reported exposures to infected poultry, livestock, or consumption of raw (unpasteurized) milk or meat, but did roam freely outdoors, so exposure to wild birds or other animals is unknown.

Clinical signs in cats can include:

-- General signs: Loss of appetite, fever, lethargy

-- Respiratory signs: Discharge from the eyes and mouth, sneezing, coughing, difficulty breathing

-- Neurologic signs: Seizures, circling, wobbling gait, blindness.

New Jersey residents should contact their veterinarian immediately if they are concerned that their cat may have H5 bird flu. Anyone who suspects a possible exposure or who has H5 HPAI concerns about their cat should contact their veterinarian prior to bringing the cat in to be seen so that the veterinarian can take the necessary precautions to prevent spread of disease. Residents who observe a sick stray or feral cat should contact their local animal control for assistance.

Veterinarians who suspect H5 HPAI in a cat should follow CDC recommendations to help protect themselves and prevent exposures, including wearing personal protective equipment (PPE) when handling the cats. All suspect feline cases should be reported to the New Jersey Department of Health Communicable Disease Service at 609-826-4872 or zoonoticrn@doh.nj.gov. Testing for suspect feline cases is available at the New Jersey Animal Health Diagnostic Laboratory, a member of the USDA’s National Animal Health Laboratory Network. Guidance for veterinarians on specimen collection and submission can be found here.

New Jersey residents can find additional information and recommendations on ways to help prevent H5 bird flu infection in cats from the American Veterinary Medical Association.

Additionally, cat owners can take the following steps to help protect their pets:

-- Do not feed cats raw (unpasteurized) milk or dairy products, and avoid feeding any raw or undercooked meat treats or diets.

-- Keep cats indoors to prevent exposure to birds and other wildlife.

-- Keep cats away from livestock, poultry, and their environments.

-- Avoid contact with sick or dead birds and other wildlife yourself.

-- Thoroughly wash your hands after handling your cat and after any encounters with poultry, livestock, or wild birds and other animals.

-- Change your clothes and shoes, and thoroughly wash any exposed skin, after interacting with sick or dead animals that may harbor the H5N1 virus, and before interacting with your cat.

-- Contact a veterinarian if you notice signs of H5 HPAI or think your cat might have been exposed to the virus.

“The H5N1 virus has the ability to move from one species to another,” New Jersey Agriculture Secretary Ed Wengryn said. "That is why we have worked closely with our poultry and dairy industries on biosecurity measures to prevent exposure by wild animals, and feral cats are another example of the risks to livestock and humans.”

“Despite low risk to the public, avian influenza is believed to be present in wild birds in all of New Jersey’s counties,” Environmental Protection Commissioner Shawn M. LaTourette said. “The Department of Environmental Protection continues to work closely with state and federal partners to track and respond to avian flu in wild birds and keep the public informed.” 

NJDOH continues to work in collaboration with the NJ Department of Environmental Protection (NJDEP) and the NJ Department of Agriculture (NJDA) to monitor occurrences of H5N1 Avian Influenza and its impact in the State.

If you find sick or dead wild birds, do not handle them. Contact the NJDEP’s Fish and Wildlife hotline at 1-877-WARNDEP. 

To report sick or dead poultry, do not handle them. Contact the NJDA Division of Animal Health at 609-671-6400. 

Additional Resources

- NJ.gov - H5N1 Information: nj.gov/H5N1

- NJ Department of Health, Communicable Disease Service - Novel Influenza: nj.gov/health/cd/topics/novel_flu.shtml

- NJ Department of Agriculture, Animal Health Diagnostic Laboratory - Contact Information: nj.gov/agriculture/ahdl/contact

- Centers for Disease Control and Prevention - Avian Influenza (Bird Flu): cdc.gov/bird-flu/hcp/animals/index.html

- American Veterinary Medical Association - Avian influenza A (H5N1) in cats: avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza/avian-influenza-h5n1-cats

Source: Department of Health, https://www.nj.gov/health/news/2025/approved/20250228a.shtml

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

This is a farm with pheasants for game restocking. The birds are being euthanized 27 February  A protection zone (3km) and a surveillance zone (10 km) have been put in place around the infected farm and all other restrictions and necessary measures according to Regulation (EU) 2016/429 and (EU) 2020/687.

Source: WOAH, https://wahis.woah.org/#/in-review/6297

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#Recommendations announced for #influenza #vaccine #composition for the 2025-2026 northern hemisphere influenza season

The World Health Organization (WHO) today announced the recommendations for the viral composition of influenza vaccines for the 2025-2026 influenza season in the northern hemisphere. 

The announcement was made at an information session at the end of a 4-day meeting on the Composition of Influenza Virus Vaccines, a meeting that is held twice annually. 

WHO organizes these consultations with an advisory group of experts gathered from WHO Collaborating Centres and WHO Essential Regulatory Laboratories to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS). 

The recommendations issued are used by the national vaccine regulatory agencies and pharmaceutical companies to develop, produce, and license influenza vaccines for the following influenza season. 

The periodic update of viruses contained in influenza vaccines is necessary for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.

The WHO recommends that trivalent vaccines for use in the 2025-2026 northern hemisphere influenza season contain the following: 

-- Egg-based vaccines

- an A/Victoria/4897/2022 (H1N1)pdm09-like virus;

- an A/Croatia/10136RV/2023 (H3N2)-like virus; and

- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.

-- Cell culture-, recombinant protein- or nucleic acid-based vaccines

- an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;

- an A/District of Columbia/27/2023 (H3N2)-like virus; and

- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus. 

The recommendation for the B/Yamagata lineage component of quadrivalent influenza vaccines remains unchanged from previous recommendations:

- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

Source: World Health Organization, https://www.who.int/news/item/28-02-2025-recommendations-announced-for-influenza-vaccine-composition-for-the-2025-2026-northern-hemisphere-influenza-season

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {Feb. 28 '25}

 

{Excerpt}

Time Period: February 16 - February 22, 2025

-- H5 Detection: 10 sites (2.6%)

-- No Detection: 379 sites (97.4%)

-- No samples in last week: 75 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

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A replicating #recombinant #VSV #model for dairy #cattle #H5N1 #influenza virus glycoprotein #evolution

Abstract

A panzootic of highly pathogenic avian influenza (HPAI) H5N1 viruses from clade 2.3.4.4b has triggered a multistate outbreak in United States dairy cattle and an unknown number of human infections. HPAI viruses are handled in specialized biocontainment facilities. Ethical considerations limit certain experimental evolution experiments aimed at assessing viral resistance to potential therapeutics. We have developed a replicating recombinant vesicular stomatitis virus (rVSV) where we replaced its glycoprotein with the hemagglutinin (HA) and neuraminidase (NA) genes of a 2.3.4.4b H5N1 virus (rVSV-H5N1dc2024), which is free of these constraints. This virus grows to high titers and encodes a fluorescent reporter to track infection. We demonstrate the utility of rVSV-H5N1dc2024 in neutralization experiments, evaluating antibody escape and characterization of resistance mutations to NA inhibitors. rVSV-H5N1dc2024 or similar viruses may accelerate efforts to develop and evaluate interventions against this emerging threat to human and animal health.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.27.640582v1

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Novel #human #coronavirus in an #infant #patient with #pneumonia, Republic of #Korea

ABSTRACT

Coronaviruses (CoVs) pose a significant threat to public health, causing a wide spectrum of clinical manifestations and outcomes. Beyond precipitating global outbreaks, Human CoVs (HCoVs) are frequently found among patients with respiratory infections. To date, limited attention has been directed towards alphacoronaviruses due to their low prevalence and fatality rates. Nasal swab and serum samples were collected from a paediatric patient, and an epidemiological survey was conducted. Retrospective surveillance investigated the molecular prevalence of CoV in 880 rodents collected in the Republic of Korea (ROK) from 2018 to 2022. Next-generation sequencing (NGS) and phylogenetic analyses characterized the novel HCoV and closely related CoVs harboured by Apodemus spp. On 15 December 2022, a 103-day-old infant was admitted with fever, cough, sputum production, and rhinorrhea, diagnosed with human parainfluenza virus 1 (HPIV-1) and rhinovirus co-infection. Elevated AST/ALT levels indicated transient liver dysfunction on the fourth day of hospitalization. Metagenomic NGS (mNGS) identified a novel HCoV in nasal swab and serum samples. Retrospective rodent surveillance and phylogenetic analyses showed the novel HCoV was closely related to alphacoronaviruses carried by Apodemus spp. in the ROK and China. This case highlights the potential of mNGS to identify emerging pathogens and raises awareness of possible extra-respiratory manifestations, such as transient liver dysfunction, associated with novel HCoVs. While the liver injury in this case may be attributable to the novel HCoV, further research is necessary to elucidate its clinical significance, epidemiological prevalence, and zoonotic origins.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2466705

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#DRC deepens #investigation on #cluster of #illness and #community #deaths in #Equateur province

Kinshasa – Health authorities in the Democratic Republic of the Congo and experts from World Health Organization (WHO) are carrying out further investigations to determine the cause of another cluster of illness and community deaths in Equateur province. 

In recent months, disease surveillance has identified increases in illness and deaths three times in different areas of the country, and triggered follow-up investigations to confirm the cause and provide needed support.  

Since the beginning of 2025, a series of illnesses and community deaths have affected Equateur province. The most recent cluster occurred in the Basankusu health zone, where last week 141 additional people fell ill, with no deaths reported. In the same health zone, 158 cases and 58 deaths were reported in the same health zone earlier in February. In January, Bolamba health zone reported 12 people who fell ill including 8 deaths. 

Increased disease surveillance has identified in total of 1096 sick people and 60 deaths in Basankusu and Bolomba fitting a broad case definition that includes fever, headache, chills, sweating, stiff neck, muscle aches, multiple joint pain and body aches, a runny or bleeding from nose, cough, vomiting and diarrhoea.  

The Democratic Republic of the Congo is facing many concurrent crises and outbreaks, putting a further strain on the health sector and the population. 

In response to the latest cluster of illness, a national rapid response team from Kinshasa and Equateur including WHO health emergency experts was deployed to Basankusu and Bolomba health zones to investigate the situation and determine if there is an unusual pattern. The experts are stepping up disease surveillance, conducting interviews with community members to understand the background, and providing treatment for diseases such as malaria, typhoid fever and meningitis.  

WHO has delivered emergency medical supplies, including testing kits, and developed detailed protocols to enhance disease investigation. 

Initial laboratory analysis has turned out negative for Ebola virus disease and Marburg virus disease. 

Around half of the samples tested positive for malaria, which is common in the region. Further tests are to be carried out for meningitis. Food, water and environmental samples will also be analysed, to determine if there might be contamination. The various samples will be sent for further testing at the national reference laboratory in Kinshasa. Earlier samples turned out not to be viable and re-testing was undertaken.  

Basankusu and Bolomba are about 180 kilometres apart and more than 300 kilometres from the provincial capital Mbandaka. The two localities are reachable by road or via the Congo River from Mbandaka. This remoteness limits access to health care, including testing and treatment. Poor road and telecommunication infrastructure are also major challenges. 

WHO is supporting the local health authorities reinforce investigation and response measures, with more than 80 community health workers trained to detect and report cases and deaths.   

Further efforts are needed to reinforce testing, early case detection and reporting, for the current event but also for future incidents. WHO remains on the ground supporting health worker, collaborating closely with zonal, provincial and national health authorities to provide lifesaving medical supplies and to coordinate response to curb the spread of the illness and other outbreaks in the region. 

Source: World Health Organization, Regional Office for Africa, https://www.afro.who.int/countries/democratic-republic-of-congo/news/democratic-republic-congo-deepens-investigation-cluster-illness-and-community-deaths-equateur

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Avian #Influenza A(#H5) Subtype in #Wastewater — #Oregon, September 15, 2021–July 11, 2024 {MMWR}

Summary

-- What is already known about this topic?

- Highly pathogenic avian influenza A(H5N1) outbreaks have emerged in U.S. cattle and poultry. Wastewater surveillance detects influenza A(H5) subtype but does not currently distinguish between human and animal sources.

-- What is added by this report?

- During September 15, 2021–July 11, 2024, retrospective analysis of wastewater surveillance data revealed 21 avian influenza A(H5) subtype detections across 12 Oregon communities. No association was found between detections in a community’s wastewater and history of a poultry outbreak or presence of dairy processing facilities or dairy farms within the sewershed. Avian influenza A(H5) was detected most frequently in two communities with important wild bird habitats.

-- What are the implications for public health practice?

- Wastewater surveillance was an early indicator of avian influenza emergence in Oregon. Nonhuman and noncattle animal inputs, including wild birds, are an essential consideration when interpreting A(H5) subtype detections in wastewater.

Abstract

Wastewater surveillance is an important tool in the surveillance of emerging pathogens and has been leveraged during the highly pathogenic avian influenza (HPAI) A(H5N1) virus outbreak in cattle and poultry in the United States. Interpretation of avian influenza A(H5) subtype detections in wastewater requires an understanding of human and animal contributors to the sewershed because current testing does not distinguish between human and animal sources. Potential animal contributors include wild birds, farms with poultry or dairy cattle outbreaks, and dairy processing facilities. Retrospective analysis of 551 influenza A virus–positive wastewater surveillance samples from 20 sites in Oregon during September 15, 2021–July 11, 2024, revealed 21 avian influenza A(H5) subtype detections across 12 communities. Avian influenza A(H5) subtype detections in wastewater began approximately 6 weeks before Oregon’s first HPAI outbreak in domestic poultry, 7 weeks before Oregon’s first avian influenza A(H5) detection in wild birds, and 2 years before the first HPAI A(H5N1) outbreak in dairy cattle in the United States (Oregon has not detected HPAI A(H5N1) in dairy cattle or milk). No association was found between detection of avian influenza A(H5) in a community’s wastewater and history of an HPAI A(H5) outbreak among poultry in the county or presence of dairy processing facilities or dairy farms within the sewershed. Avian influenza A(H5) was detected most frequently in two communities with important wild bird habitats. Animal inputs, including from wild birds, should be considered when interpreting avian influenza A(H5) subtype detections in wastewater.

Source: US Centers for Disease Control and Prevention, MMWR, https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a5.htm?s_cid=mm7406a5_w&ACSTrackingID=USCDC_921-DM145368&ACSTrackingLabel=This%20Week%20in%20MMWR%3A%20Vol.%2074%2C%20February%2027%2C%202025&deliveryName=USCDC_921-DM145368

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#Pandemic #risk stemming from the #bovine #H5N1 #outbreak: an account of the #knowns and #unknowns

ABSTRACT

H5N1 subtype influenza A viruses represent a long-standing pandemic concern. Owing to their global occurrence in poultry, humans are routinely exposed to these viruses, and hundreds of human cases have been documented worldwide since 2003. The relevant viral lineages are not static, however, and have recently undergone a massive expansion of host range and geographic distribution. Within this expansion, the introduction of H5N1 viruses into dairy cattle in the United States has spawned a novel animal-human interface. In response, public health agencies have sought to evaluate the risk of an H5N1 pandemic stemming from the bovine outbreak. These assessments draw on evidence from the field and the laboratory to score a series of recognized risk factors. As such, their utility hinges on fundamental understanding of the processes that drive pandemic emergence and the availability of relevant data. Advancing this understanding and gathering data prior to and during an outbreak are primary missions of the NIAID Centers of Excellence for Influenza Research and Response (CEIRR) Network. To further these goals and highlight the need for an invigorated response across US agencies, here, we review gaps in understanding of the dairy cattle outbreak and identify constraints on efforts to close these gaps.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00052-25?af=R

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Evaluating #Probenecid or #Oseltamivir #Inhibition of #Influenza A Virus #Replication Through Plaque Assay or Fluorescent Focus Assay Using NS1–H1N1 Venus Reporter Virus

Abstract

It is essential to understand the molecular mechanisms of influenza antiviral therapeutics to evaluate their efficacy. Virus plaque assays are commonly used to assess the antiviral effects of drugs on virus replication; however, this method is labor-intensive and can present challenges. We avoided this method by using a replication-competent influenza A virus (IAV) expressing a reporter fluorescent gene fused to the non-structural protein 1 (NS1) gene. The reporter IAV was detectable in normal human bronchoepithelial (NHBE) infected cells and offered an improved method to determine the therapeutic efficacy of the antiviral drugs probenecid and oseltamivir compared to a standard plaque assay. This method provides an excellent means for evaluating therapeutic approaches against IAV.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/335

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3rd #meeting of #IHR (2005) Emergency #Committee regarding upsurge of #mpox 2024 – Temporary #recommendations

{Excerpts}

The Director-General of the World Health Organization (WHO), following the third meeting of the International Health Regulations (2005) (IHR) Emergency Committee regarding the upsurge of mpox 2024, held on 25 February 2025, from 12:00 to 17:00 CET, concurs with its advice that the event continues to meet the criteria of a public health emergency of international concern and, considering the advice of the Committee, he is hereby issuing a revised set of temporary recommendations.

The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee. The proceeding of the third meeting of the Committee will be shared with States Parties to the IHR and published in the coming days.

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Temporary recommendations

These temporary recommendations are issued to States Parties experiencing the transmission of monkeypox virus (MPXV), including, but not limited to, those where there is sustained community transmission, and where there are clusters of cases or sporadic travel-related cases of MPXV clade Ib.

They are intended to be implemented by those States Parties in addition to the current  standing recommendations for mpox, which will be extended until 20 August 2025. 

In the context of the global efforts to prevent and control the spread of mpox disease outlined in the  WHO Strategic framework for enhancing prevention and control of mpox- 2024-2027, the aforementioned  standing recommendations apply to all States Parties. 

All current WHO interim technical guidance can be accessed on this page of the WHO website. WHO evidence-based guidance has been and will continue to be updated in line with the evolving situation, updated scientific evidence, and WHO risk assessment to support States Parties in the implementation of the WHO Strategic Framework for enhancing mpox prevention and control. 

Pursuant to Article 3 Principle of the International Health Regulations (2005) (IHR), the implementation of these temporary recommendations, as well as of the standing recommendations for mpox, by States Parties shall be with full respect for the dignity, human rights and fundamental freedoms of persons, in line with the principles set out in Article 3 of the IHR. 

(...)

Source: World Health Organization, https://www.who.int/news/item/27-02-2025-third-meeting-of-the-international-health-regulations-2005-emmergency-committee-regarding-the-upsurge-of-mpox-2024-temporary-recommendations

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Quantitative #risk #assessment of #human #H5N1 #infection from #consumption of fluid #cow's #milk

Abstract

The spillover of highly pathogenic avian influenza H5N1 into dairy cattle has raised concerns over the safety of fluid milk. While no human foodborne infection has been reported, this strain has infected dozens of people and milk from infected cows is known to be infectious by ingestion in multiple other species. Investigation into the public health threat of this outbreak is critical. This study uses quantitative risk assessment (QRA) models to represent the United States raw and pasteurized fluid milk supply chains to estimate the risk of human infection from consumption of fluid cow's milk. These models were parameterized with literature emerging from this outbreak, then employed to estimate the H5N1 infection risk and evaluate multiple potential interventions aimed at reducing this risk. The median (5th, 95th percentiles) probabilities of infection per 240-mL serving of pasteurized, farmstore-purchased raw, or retail-purchased raw milk were 5.68E-15 (1.77E-16, 2.98E-13), 1.13E-03 (5.16E-06, 3.82E-02), and 1.02E-03 (5.20E-06, 3.64E-02), respectively. Our results demonstrate that pasteurization is highly effective at reducing H5N1 infection risk. Scenario analysis revealed quantitative real-time reverse transcriptase-polymerase chain reaction (qrRT-PCR) testing of bulk tank milk to be an effective method for reducing risk from raw milk. Additionally, we identify knowledge gaps related to human H5N1 dose-response by ingestion and raw milk consumption patterns. These findings emphasize the importance of pasteurization in protecting public health and will inform the implementation of control strategies to reduce the risk of human H5N1 infection from raw milk.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.12.20.24319470v2

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Immunogenicity and protective #efficacy of an #intranasal NA-based #influenza virus #vaccine adjuvanted ...

Abstract

Influenza virus neuraminidase (NA) has emerged as a promising vaccine candidate due to its relatively stable antigenic structure and the ability of NA-specific antibodies to provide cross-protection within influenza virus subtypes. Since the influenza virus causes respiratory infections in humans, developing mucosal vaccines to protect the entry site of the virus is of high importance. Recombinant NA requires adjuvants to induce a protective immune response after mucosal administration. In the current study, we analyze the immunogenicity and protective efficacy of a recombinant NA-based influenza virus vaccine administered intranasally in combination with adjuvants consisting of outer membrane proteins from Neisseria meningitidis complexed with exogenous lipopolysaccharides (LPS) from Shigella flexneri or endogenous LPS from N. meningitidis. We evaluated the local and systemic humoral and cellular immune responses to adjuvanted recombinant N1 NA, analyzing the dynamics of local follicular T-helper (Tfh) cells and germinal center B cells (GCB) in nasal-associated lymphoid tissue (NALT) and tissue-resident memory T cells in lungs, as well as the levels of IgA and IgG in the upper and lower respiratory tracts. Finally, we performed a heterologous challenge study to test the ability of the investigated vaccine formulations to induce cross-protection. The study demonstrates that bacterial cell membrane-derived adjuvants significantly improve the immunogenicity and protective efficacy of the recombinant N1 NA-based influenza vaccine leading to protection against clade 2.3.4.4b H5N1 challenge. This finding supports the potential of these adjuvanted vaccines in providing effective mucosal immunity against influenza virus.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.26.640278v1

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#USA, #Influenza A #H5N1 in #Humans: #Epidemiology & #Laboratory #Update {as of Feb. 26 '25}

{Excerpts}

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Epidemiology Updates

As of February 24, CDC has confirmed three human cases of H5 bird flu in people who became ill in 2025: 

-- a dairy worker with exposure to infected dairy cows (Nevada), 

-- a poultry worker with exposure to infected commercial poultry (Ohio), and 

-- the owner of an infected backyard poultry flock (Wyoming). 

These are all considered higher-risk exposures. While the dairy worker was not hospitalized, both people with poultry exposures experienced severe illness and were hospitalized. Both hospitalized cases were confirmed positive from lower respiratory specimens, including a bronchoalveolar lavage and sputum. To date, there has been no evidence of onward spread from any of these people to anyone else.

The dairy worker in Nevada had conjunctivitis (eye redness and irritation) and has recovered. Most infections associated with U.S. dairy cows to date have involved mild respiratory symptoms or conjunctivitis. This person was exposed to infected dairy cows and tested positive for avian influenza A(H5N1) virus.

The poultry worker in Ohio had respiratory symptoms and is home and recovering. This person participated in culling activities on a farm with infected poultry. The initial upper respiratory specimens could not be confirmed as positive for avian influenza A(H5) virus at CDC, so CDC initially reported this as a probable case; a subsequent specimen from the person was confirmed positive for avian influenza A(H5) virus at CDC.

The backyard flock owner in Wyoming had respiratory symptoms and is reported to have underlying health conditions that can make people more vulnerable to severe influenza illness. This person has been discharged from the hospital and is recovering. This person had direct contact with poultry infected with avian influenza A(H5) virus that died on their property. Initial upper respiratory specimens were negative for influenza viruses; a lower respiratory specimen collected several days later in the hospital was positive for avian influenza A(H5N1) virus.

Laboratory Updates

CDC has successfully sequenced the viruses from the Nevada and Wyoming cases. Genetic data have been posted in GISAID (Wyoming: EPI_ISL_19749443, Nevada: EPI_ISL_19726293) and GenBank. Sequencing data are not yet available for the Ohio case.

CDC's analysis of the genetic sequence of the virus isolated from the patient in Nevada identified the virus as an avian influenza A(H5N1) virus from clade 2.3.4.4.b (genotype D1.1). The nucleotide sequence was nearly identical to that of the viruses that USDA reported from dairy cows in Nevada that the person worked with. The virus had a genetic mutation in its polymerase basic 2 (PB2) protein that has previously been associated with more efficient virus replication in mammalian cells (i.e., change of PB2 D701N). This change was previously identified in a human case in Chile in 2023. No other changes associated with mammalian adaption were identified in the sequence data. CDC also did not identify any changes that might impact effectiveness of influenza antiviral medications or existing clade 2.3.4.4b H5 candidate vaccine viruses.

CDC's analysis of the genetic sequence of the virus from the patient in Wyoming identified an avian influenza A(H5N1) virus from clade 2.3.4.4.b (genotype D1.1). The virus had a genetic mutation in its PB2 protein that has previously been associated with more efficient virus replication in people and other mammals (i.e., change of PB2 E627K). This change was previously identified in a human case in Texas during 2024. No other changes associated with mammalian adaption were identified in the sequence data. CDC also did not identify any changes in the sequence data that might impact effectiveness of influenza antiviral medications or existing H5 candidate vaccine viruses. Virus was isolated from the case and will undergo further testing and analysis.

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/h5n1-response-02262025.html

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Clade 2.3.4.4b #H5N1 #neuraminidase has a long #stalk, which is in contrast to most highly pathogenic H5N1 viruses circulating between 2002 and 2020

ABSTRACT

Since 2020, H5N1 highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4b have been rapidly spreading in wild birds but have also caused a large number of mammalian infections and more than 70 known human cases. Importantly, this H5N1 clade has also crossed the species barrier into dairy cattle in the US in late 2023/early 2024. The neuraminidase (NA) protein of the N1 subtype can feature truncations in its stalk domain, which have been identified as putative virulence factors in poultry but seem to have a negative impact on transmission in mammals. Since its emergence, the vast majority of HPAI H5N1 A/goose/Guangdong/1/1996-lineage isolates have featured this truncated version of the NA stalk domain. Here, we report that this changed with the 2020 expansion of clade 2.3.4.4b H5N1 and that the majority of isolates—including the strains circulating in dairy cattle—feature a long NA stalk domain.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.03989-24

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#Host #cell entry and #neutralisation sensitivity of the emerging #SARS-CoV-2 #variant #LP.8.1

{Excerpt}

Novel SARS-CoV-2 variants continue to emerge, driving waves of COVID-19. The evolution of SARS-CoV-2 took a surprising turn in 2023 with the emergence of BA.2.86, a BA.2-descendant harbouring multiple spike (S) protein mutations, enhancing antibody evasion. Subsequently, several BA.2.86-derived lineages emerged, with JN.1 dominating early and the JN.1-derived variants KP.3.1.1 and XEC dominating late in 2024. Currently, LP.8.1 is on the verge of becoming dominant. This study provides a preliminary virological characterisation of LP.8.1 and its sublineage LP.8.1.1.

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Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00113-6/fulltext?rss=yes

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