Wednesday, March 19, 2025

Large-scale computational #modelling of #H5 #influenza #variants against #HA1-neutralising #antibodies

Summary

Background

The United States Department of Agriculture has recently released reports that show samples collected from 2022 to 2025 of highly pathogenic avian influenza (H5N1) have been detected in mammals and birds. Up to February 2025, the United States Centres for Disease Control and Prevention reports that there have been 67 humans infected with H5N1 since 2024 with 1 death. The broader potential impact on human health remains unclear.

Methods

In this study, we computationally model 1804 protein complexes consisting of various H5 isolates from 1959 to 2024 against 11 haemagglutinin domain 1 (HA1)-neutralising antibodies. This was performed using AI-based protein folding and physics-based simulations of the antibody-antigen interactions. We analysed binding affinity changes over time and across various antibodies using multiple biochemical and biophysical binding metrics.

Findings

This study shows a trend of weakening binding affinity of existing antibodies against H5 isolates over time, indicating that the H5N1 virus is evolving immune escape from our therapeutic and immunological defences. We also found that based on the wide variety of host species and geographic locations in which H5N1 was observed to have been transmitted from birds to mammals, there is not a single central reservoir host species or location associated with H5N1's spread.

Interpretation

These results indicate that the virus has potential to move from epidemic to pandemic status. This study illustrates the value of high-performance computing to rapidly model protein–protein interactions and viral genomic sequence data at-scale for functional insights into medical preparedness.

Source: EBioMedicine, https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00076-3/fulltext

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Different #genetic #determinants for high #virulence, #transmission and #replication of high pathogenicity #H7N7 avian #influenza virus in #turkeys and #chickens

Abstract

High pathogenicity (HP) avian influenza viruses (AIV) generally evolve from low pathogenicity (LP) precursors after transmission from wild birds to chickens (Gallus gallus domesticus) and turkeys (Meleagris gallopavo), causing severe economic losses worldwide. Turkeys are more susceptible to AIV infection than chickens and are considered potential bridging hosts that facilitate the emergence of HPAIV. Beyond the polybasic cleavage site (pCS) in hemagglutinin (HA), little is known about other virulence determinants of HPAIV in these species. In 2015, HPAIV H7N7 and its LP ancestor were isolated from the same chicken farm, which differed by 16 nonsynonymous mutations across all eight gene segments, in addition to the pCS. Here we identify the genetic determinants, including the pCS, that contributed to the HPAIV H7N7 virulence, transmission, replication, and tissue distribution in chickens and turkeys. Notably, the non-structural (NS1) or matrix (M) proteins’ encoding segments in turkeys, or NS segment in chickens, rendered viruses as virulent and transmissible as the original HPAIV. Endotheliotropism, observed exclusively in chickens, was driven by the pCS and, to a lesser extent, the neuraminidase (NA). In vitro, the M2-V68L mutation influenced NS1 expression and virus morphology in chicken and turkey cells. Additionally, HPAIV NS1 enhanced polymerase activity and effectively suppressed interferon induction, a process further modulated by M2-V68L. These findings underscore the critical role of turkeys as a “hub” in the evolution of HPAIV from LP precursors, offering crucial insights into the genotypic and phenotypic factors that facilitate viral adaptation in different poultry species.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.18.643940v1?rss=1

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Tuesday, March 18, 2025

#Baloxavir improves #disease #outcomes in #mice after intranasal or ocular #infection with #Influenza A virus #H5N1-contaminated cow’s #milk

Abstract

Testing approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species, including dairy cows, is critical to public health and pre-pandemic planning. It cannot be tested in humans due to A(H5N1) disease severity. Here, in mice, we demonstrate that US FDA-approved baloxavir treatment mediates improved disease outcomes (survival and viral dissemination) over oseltamivir after lethal intranasal and ocular challenge with A(H5N1)-contaminated cow milk.

Source: Nature Microbiology, https://www.nature.com/articles/s41564-025-01961-5

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

A poultry farm in Telangana Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6323

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Analyses of #phylogenetics, natural #selection, and #protein structure of clade 2.3.4.4b #H5N1 #Influenza A reveal that recent viral lineages have evolved promiscuity ...

Abstract

H5N1 influenza has been circulating in birds from Eurasia and Africa for more than 146 years, but human infection has been sporadic. H5N1 (clade 2.3.4.4b) has recently infected hundreds of species of wild and domestic birds and mammals in North America. Furthermore, as of February 26, 2025, H5N1 has infected 70 humans in the United States, and one infection proved lethal. Furthermore, in attempts to control H5N1 in the United States, 10s of millions of egg-laying chickens have died or been culled. These efforts have led to very high egg prices in the United States. We have developed an analytical bioinformatics and genomics workflow to understand better how H5N1 is circulating in North America and adapting to new host species. Our workflow consists of: 1) Phylogenetic analyses of large viral sequence datasets to identify subclades of viral lineages causing the current outbreaks in humans and farm animals and closely related viral background lineages. 2) Next, we transfer sequence data from subclades of interest with farm animal and human infection, background data, and vaccine candidate data to analyses of natural selection. 3) Once we identify mutations of interest that underlie recent viral adaptation to animal and human infection, we perform computational structural analyses of binding to host proteins for cell receptors and immune processes. Here, we show that H5N1 (clade 2.3.4.4b) is spreading in North America as two distinct subclades of interest for human and animal health. These viral lineages have achieved a vast host range by efficiently binding the viral surface protein Hemagglutinin (HA) to both mammalian and avian receptors. This novel promiscuity of host range is concomitant with the additional strengthening of the polymerase basic 2 (PB2) viral protein's binding for mammalian and avian immune proteins. Once bound, the immune proteins are disabled, thus allowing for more efficient replication of H5N1 in mammalian and avian cells than seen in the recent past. In conclusion, H5N1 (clade 2.3.4.4b) is causing an animal pandemic through promiscuity of host rage and strengthening ability to evade the innate immune systems of both mammalian and avian cells.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.15.641219v1?rss=1

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Monday, March 17, 2025

3rd #meeting of #IHR(2005) #Emergency #Committee regarding the upsurge of #mpox 2024

The Director-General of the World Health Organization (WHO) is hereby transmitting the report of the third meeting of the International Health Regulations (2005) (IHR) Emergency Committee (Committee) regarding the upsurge of mpox 2024, held on Tuesday, 25 February 2025, from 12:00 to 17:00 CET.

Concurring with the advice unanimously expressed by the Committee during the meeting, the WHO Director-General determined that the upsurge of mpox 2024 continues to meet the criteria of a public health emergency of international concern (PHEIC) and, accordingly, on 27 February 2025, issued temporary recommendations to States Parties.

The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee.


Proceedings of the meeting

Sixteen (16) Members of, and two Advisors to, the International Health Regulations (2005) (IHR) Emergency Committee (Committee) were convened by teleconference, via Zoom, on Tuesday, 25 February 2025, from 12:00 to 17:00 CET. Fourteen (14) of the 16 Committee Members, and one of the two Advisors to the Committee participated in the meeting.

On behalf of the Director-General of the World Health Organization (WHO), the Deputy Director-General welcomed Members of and Advisors to the Committee, as well as Government Officials designated to present their views to the Committee on behalf of the ten invited States Parties Burundi, Canada, China, the Democratic Republic of the Congo (DRC), Nepal, Nigeria, Rwanda, Sierra Leone, Uganda, United Arab Emirates and United Kingdom of Great Britain and Northern Ireland (United Kingdom).

In his opening remarks, the WHO Deputy Director-General recalled that, on 14 August 2024, the upsurge of mpox was determined to constitute a public health emergency of international concern (PHEIC). He noted that, over the three years from 1 January 2022 through 31 January 2025, almost 130 000 confirmed cases of mpox, including over 280 deaths, were reported to WHO from 130 countries and territories in all six WHO Regions, including seven countries and territories that had reported their first mpox cases since the previous meeting of the Committee on 22 November 2024. The WHO African Region, where some States Parties are continuing to experience sustained community transmission, accounts for 61% of the cases and 72% of the deaths reported globally over the past 12 months.

The WHO Deputy Director-General highlighted that, since the last meeting of the Committee, the epidemiological situation continues to be volatile. Despite observed improvements pertaining to several aspects of the response – emergency coordination, surveillance, laboratory diagnostics, empowerment of communities, furthering equitable access to medical countermeasures and tools – several critical challenges had emerged, including: 

-- (a) rising geopolitical instability in the DRC due to escalating conflict affecting mpox response operations resulting in temporary pauses in operation, relocation of staff and restricted access to affected populations; 

-- (b) concurrent health emergencies requiring States Parties and partners to respond (e.g. Sudan virus disease outbreak in Uganda); and 

-- (c) uncertainties related to the pause in financial support from the United States of America (United States) occurring in the broader landscape of declining foreign assistance. 

To date, globally, one-third of the funds supporting the response to mpox had been pledged by the United States. Without sufficient funds, the ability of States Parties, WHO and partners to maintain, sustain, and expand the response to mpox would be compromised.

The Representative of the Office of Legal Counsel then briefed the Members and Advisors on their roles and responsibilities and identified the mandate of the Committee under the relevant articles of the IHR. The Ethics Officer from the Department of Compliance, Risk Management, and Ethics provided the Members and Advisors with an overview of the WHO Declaration of Interests process. The Members and Advisors were made aware of their individual responsibility to disclose to WHO, in a timely manner, any interests of a personal, professional, financial, intellectual or commercial nature that may give rise to a perceived or actual conflict of interest. They were additionally reminded of their duty to maintain the confidentiality of the meeting discussions and the work of the Committee. Each Member and Advisor was surveyed, with no conflicts of interest identified.

The meeting was handed over to the Chair who introduced the objectives of the meeting, which were to provide views to the WHO Director-General on whether the event continues to constitute a PHEIC, and if so, to provide views on the potential proposed temporary recommendations.


Session open to representatives of States Parties invited to present their views

The WHO Secretariat presented an overview of the global epidemiological situation of mpox, including all circulating clades of monkeypox virus (MPXV). Outside the WHO African Region, cases of mpox reported to WHO are associated with the spread of MPXV clade IIb, with a decline in the number of cases reported in recent months. In the WHO African Region, amid the circulation of multiple MPXV clades, the still growing number of cases reported monthly is driven by the spread of MPXV clade Ib. Since the Committee last met, on 22 November 2024, exported travel-related cases of confirmed MPXV clade Ib infection have been detected in eight additional countries outside the WHO African Region.

The WHO Secretariat then focused on the three countries reporting most cases of MPXV clade Ib since January 2024 – the DRC (over 15 000 cases, including cases in areas where MPXV clade Ia is circulating); Burundi (over 3000 cases, with a sustained decrease reported weekly and a geographic shift to the administrative capital Gitega since the Committee last met); and Uganda (nearly 3000 cases, with an exponential increase in and around the capital Kampala since the Committee last met). Notwithstanding changes in the case definition of mpox cases, uneven surveillance coverage (including due to the conflict in the eastern provinces of the country), and limited laboratory testing capacity in the DRC introducing some challenges in the interpretation of data , the number of mpox cases reported weekly is plateauing and the geographic distribution of cases, in all provinces in the country, remained very similar to the situation presented at the previous meeting of the Committee. Mathematical modelling work suggests that, since the PHEIC was determined in mid-August 2024 in the DRC, the transmission rate has decreased in certain health zones of the North Kivu and South Kivu Provinces, as well as in some health zones of the capital Kinshasa where vaccination efforts are underway.

The spread of MPXV clade Ia and Ib, in North Kivu, South Kivu, and Kinshasa Provinces of the DRC, as well as in Burundi and Uganda, appears to have started among adults, including through sexual networks involving commercial sex workers and their clients, disproportionately affecting the 20–39 years age group. Since then, in North Kivu and South Kivu Provinces of the DRC, more age group became affected reflecting community transmission through close contact, including household, whereas, in the capital Kinshasa, the spread has remained within the adult population. In Burundi and Uganda, the age distribution of mpox cases shows a bimodal pattern, with high incidence observed among young adults and younger children. This pattern reflects both ongoing sexual transmission and close contact transmission in household settings. The strikingly high proportion of cases among younger children (0-9 age group) observed in Burundi is possibly attributable to transmission occurring within health care facilities settings.

In addition to the three aforementioned countries, community transmission of MPXV clade Ib is also observed in Kenya, Rwanda, and Zambia, while travel-related imported cases have been reported both, by countries in the WHO African Region (Angola, Zimbabwe, with cases in Tanzania being under investigation), and by 14 countries in the five remaining WHO Regions. Most travel-related imported cases are male and, in instances where limited secondary transmission in the country of importation has occurred, a few children have been infected through household contact, including child-to-child transmission on one occasion. The five imported cases with sole travel history to the United Arab Emirates may signal wider mpox transmission in that country.

Mortality associated with the different MPXV clades in the WHO African Region, and notwithstanding the limitation of surveillance and laboratory diagnostics in the DRC, clade Ia accounts for the majority of fatal cases (1345), corresponding to an average case fatality rate (CFR%) of 2.5-3%, being highest in children under 1 year of age (4–5%). The CFR attributed with clade Ib infection remains very low at around 0.2%, and similar to the that attributed to clade IIb, with recorded deaths associated with specific risk factors such as uncontrolled HIV and other comorbidities.

The WHO Secretariat also noted an increase in mpox cases reported in West African countries since the PHEIC was determined in mid-August 2024, including the first cases of mpox, due to MPXV clade IIa, reported by Sierra Leone.

The WHO Secretariat presented the assessed risk by MPXV clades and further expressed in terms of overall public health risk where any given clade/s is/are circulating, as: 

-- Clade Ib – high public health risk in the DRC and neighbouring countries; 

-- Clade Ia – moderate public health risk in the DRC

-- Clade II – moderate public health risk in Nigeria and countries of West and Central Africa where mpox is endemic; and 

-- clade IIb – moderate public health risk globally.

The WHO Secretariat subsequently provided an update on response actions taken together with States Parties and partners since the Committee last met. In addition to the overview provided by the WHO Deputy Director-General, and in the epidemiological overview, the WHO Secretariat provided details on progress and challenges focusing on the aspects of the response outlined below.

The coordination of emergency operations by the WHO Secretariat was readjusted – including based on action reviews and leveraging the comparative advantages of WHO, State Parties, and partners –prioritizing a flexible, agile, and delivery-focused response. However, while decentralized field operations have intensified, such shifts take time, particularly in specific settings in the DRC and amid changes in geopolitical partnerships. The operational decentralization continues to emphasize increased laboratory diagnostic support, increased dissemination of standards and guidance to deliver safe clinical care, and empowering communities to enhance their efforts to protect themselves from risks associated with mpox.

Additionally, through the Access and Allocation Mechanism (AAM), WHO and partners (Africa Centres for Disease Control and Prevention (Africa CDC), the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi, The Vaccine Alliance (Gavi), and the United Nations Children’s Fund (UNICEF)) are continuing coordinated and multifaceted efforts to prioritize access to and roll out mpox vaccines in an equitable manner.

With the WHO Mpox global strategic preparedness and response plan, September 2024-February 2025 (SPRP) reaching the end of its initial timeframe, and considering the response strategy it outlines as still fit for purpose, the WHO Secretariat is planning to release an extension of the plan in the coming weeks.

In September 2024, the WHO Secretariat launched an appeal for US$ 87.4 million to support mpox response efforts WHO appeal: mpox public health emergency 2024 with US$ 65.5 million raised by the time of this meeting. The contribution from the United States had accounted for 33% of the funds raised, of which US$ 7.5 million is currently inaccessible due to the freeze of funds from the United States. As part of planning for the extension of the SPRP, the WHO Secretariat is conducting a review of available resources to address priority needs and mitigate potential future gaps in the delivery of the response. While the above-mentioned freeze is expected to primarily impact operations in Burundi, the Central African Republic, the DRC, the Republic of the Congo, and Rwanda, broader challenges are anticipated for the second and third quarters of 2025. Given the evolving epidemiological situation and challenges noted above, the reduction in predictable and flexible funding throughout 2025 will put at risk the progress of the mpox response to date.

Representatives of Burundi, the DRC, Nigeria, Sierra Leone, and Uganda updated the Committee on the mpox epidemiological situation in their countries and their current control and response efforts, needs and challenges, including those related to the freeze of the funds from the United States. The use of mpox vaccine is contemplated in the response plans of the DRC, Nigeria, Sierra Leone, and Uganda. In Burundi, following action review, community-based interventions that are being strengthened in areas experiencing high incident of mpox include risk communication and awareness raising.

Members of, and the Advisor to, the Committee then engaged in questions and answers, revolving around the issues and challenges enumerated below, with the presenters from States Parties and the WHO Secretariat, as well as with representatives of States Parties invited to submit a written statement to the Committee ahead of the meeting – Canada, China, Nepal, the United Arab Emirates, and the United Kingdom.

FundingThe Committee reiterated the importance of efforts to mobilize domestic financial resources to support mpox response activities. Burundi and the DRC indicated the funds allocated to the response by their respective Governments, also providing details of specific activities supported. The DRC indicated that, at present, the freeze of the funds from the United States is impacting the transportation of clinical specimens and laboratory diagnostics, with a decline in the testing rate, and that the Government is exploring solutions with other partners. The WHO Secretariat added that alternative funding sources are being explored with non-traditional donors.

Age distribution of mpox casesThe WHO Secretariat indicated that 

- (a) there are studies ongoing to determine the secondary attack rate by age group and type of exposure; 

- (b) at least in Burundi, there is no evidence of large outbreaks in settings where children are congregating and, hence, supporting evidence of child-to-child transmission; and 

- (c) in the South Kivu Proving of the DRC, it remains unknown the extent to which transmission to children is occurring beyond the household setting.

Impact of vaccination on transmissionThe DRC indicated that, at present, there is no information about whether the use of the limited amount of mpox vaccine available is being effective in interrupting mpox transmission.

The DRC – The DRC indicated that, due to insecurity and to decrease in laboratory testing rate, any apparent decrease of the number of reported mpox cases may represent an artifact and should be interpreted with caution. The WHO Secretariat highlighted that, being mpox a relatively mild illness, the rate of underreporting is unknown and that the trends of mpox surveillance data are critical to monitor the evolution of the situation. With respect to detection of a new MPXV clade Ia lineage in Kinshasa, the WHO Secretariat indicated that the strain, similarly to clade Ib, has increased human-to-human transmission potential.

UgandaUganda elaborated on the shift of the dynamics of mpox transmission from lower to higher income groups. The initial spread of MPXV clade Ib initiated long-distance truck drivers, it continued in fishing communities, and then within commercial sex networks in the capital Kampala. The fact that more affluent individuals are now affected poses a public health risk both, nationally and internationally. Therefore, the use of mpox vaccine is focused among sex workers in Kampala.

NigeriaNigeria indicated that, in the context of the mpox response, the human health and animal health sectors are working very closely and that, despite the numerous research initiatives, to date, there is no evidence of animal involvement in sustaining the mpox outbreak in the human population. Nigeria, with a population of 200 million persons, indicated that 20 000 doses of mpox vaccine have been used in the country, targeting health care workers, female sex workers, and men who have sex with men.

The United Arab EmiratesConsidering that, in five instances, travel-related imported cases of MPXV clade Ib infection had sole travel history to the United Arab Emirates, the representative of the country 

- (a) indicated that the National IHR Focal Point reported to WHO the first case of MPXV clade Ib infection; 

- (b) briefly described the surveillance, laboratory diagnostic, case management, and risk communication approaches in place; 

- (c) indicated that mpox vaccine is available to health care workers and as a post-exposure measure; and 

- (d) recalled that the country is bilaterally supporting the response efforts of some African countries.

The United Kingdom – The United Kingdom 

- (a) described the detection, investigation, and clinical and public health management of the travel-related imported mpox cases; and 

- (b) highlighted that the countries of origin of the imported cases are systematically informed about the occurrences.


Deliberative session

Following the session open to invited States Parties, the Committee reconvened in a closed session to examine the questions in relation to whether the event constitutes a PHEIC or not, and if so, to consider the temporary recommendations drafted by the WHO Secretariat in accordance with IHR provisions.

The Chair reminded the Committee Members of their mandate and recalled that a PHEIC is defined in the IHR as an “extraordinary event, which constitutes a public health risk to other States through the international spread of disease, and potentially requires a coordinated international response”.

The Committee was unanimous in expressing the views that the ongoing upsurge of mpox still meets the criteria of a PHEIC and that the Director-General be advised accordingly

The overarching considerations underpinning the advice of the Committee are 

- (a) the insecurity in the eastern provinces and in the capital of the DRC – the State Party epicenter of the MPXV clade Ib outbreak –, hampering mpox response field operations and with the potential to morph into a larger scale humanitarian response; 

- (b) the freeze of funding by the United States both, of specific mpox response activities as well as of other, directly or indirectly related, aid interventions; and 

- (c) the continuing detection of travel-related imported mpox cases in States Parties within and outside the WHO African Region.

On that basis, the Committee considered that:

The event is “extraordinary” because of 

- (a) the persistent, if not increasing, challenges in gauging the actual magnitude and trend of the MPXV clade Ib outbreak, especially in the DRC. This is thwarting the ability to assess progress, if any, towards controlling the spread of mpox and to adjust response interventions. The Committee’s reading is that, overall, the epidemiological situation is worryingly similar to that observed in November 2024; 

- (b) the unfolding dynamics of MPXV clade Ib transmission, resulting in the shift in age groups affected and, hence, posing challenges in timely targeting response interventions; 

- (c) the co-circulation and the risk of mutations of MPXV clades in the context of sustained community transmission; and 

- (d) the possibility of change in the severity of disease resulting from food insecurity and interruption in the delivery of HIV-related care due to the freeze of aid.

The event “constitutes a public health risk to other States through the international spread of disease” because of 

- (a) the doubling of the number of States Parties having detected travel-related imported cases of MPXV clade Ib infection since the Committee last met, both in the WHO African Region and in all five other WHO Regions; 

- (b) the possible influx of refugees from the eastern provinces of the DRC into neighbouring countries.

The event “requires a coordinated international response” because of the needs 

- (a) to mobilize, and optimize the use, of financial and other resources to sustain response efforts, at the required level, in the medium term, following the freeze of funding by the United States; and 

- (b) to continue facilitating and increasing equitable access to mpox vaccines and diagnostics.


The Committee subsequently considered the draft of the temporary recommendations proposed by the WHO Secretariat

Anticipating the possibility that the WHO Director-General may determine that the event continues to constitute a PHEIC, the Committee had received a proposed set of revised temporary recommendations ahead of the meeting. This reflected the proposal to extend most of the temporary recommendations issued on 27 November 2024. The Committee indicated that it would be giving them further consideration with a view to share its advice in that regard with the WHO Director-General as soon as possible. In such a way, should the WHO Director-General determine that the event continues to constitute a PHEIC, he could proceed, without delay, with issuing such communication together with a prospective revised set of temporary recommendations.

The Committee agreed to finalize the report of its third meeting during the week of 3 March 2025.


Conclusions

The Committee reiterated its concern regarding the continuing spread of MPXV in and beyond Africa, considering global geopolitical developments, the humanitarian situation in the DRC, as well as the foreseeable options and opportunities to secure sustainable funding to support response efforts. The Committee considered that the determination by the WHO Director-General that the upsurge of mpox still constitutes a PHEIC would be warranted. However, the Committee cautioned about the possible unintended consequences of determining an event to constitute a PHEIC for extended periods of time, since this could undermine the global public health alert function intrinsic to such a determination and reduce the leverage of a PHEIC in boosting domestic and international response efforts for future events. To that effect, the Committee reiterated the need to elaborate on considerations, related to the three criteria defining a PHEIC, that would inform its future advice to the WHO Director-General as to the termination of this PHEIC.

The Incident Manager for mpox at WHO headquarters, on behalf of the WHO Deputy Director-General, expressed his gratitude to the Committee’s Officers, its Members and Advisor and closed the meeting.

Source: World Health Organization, https://www.who.int/news/item/17-03-2025-third-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-upsurge-of-mpox-2024

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#Togo - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification [FINAL]

 A poultry farm in Centre Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6338

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#USA - High pathogenicity avian #influenza #H7N9 viruses (#poultry) (Inf. with) - Immediate notification

Highly pathogenic avian influenza (HPAI) H7N9 of North American wild bird lineage was detected in a commercial broiler breeder chicken flock in Mississippi. Depopulation of the affected flock is in progress. The USDA Animal and Plant Health Inspection Service (APHIS), in conjunction with State Animal Health and Wildlife Officials, are conducting a comprehensive epidemiological investigation and enhanced surveillance in response to the detection.

A commercial broiler breeder premises {in Mississippi}. Clinical signs included increased mortality. Depopulation was completed 13 Mar 2025.

Source: WOAH, https://wahis.woah.org/#/in-review/6340

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Sunday, March 16, 2025

Superior #replication, #pathogenicity, and immune #evasion of a #Texas dairy #cattle #H5N1 virus compared to a historical avian isolate

Abstract

The current outbreak of highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype clade 2.3.4.4b in dairy cattle in the United States has affected nearly 900 dairy farms and resulted in at least 39 human infections, putting health authorities and the scientific community on high alert. Here we characterize the virus growth properties and host-pathogen interactions of an isolate obtained from a sick dairy cow in Texas in vitro and in vivo and compare it to an older HPAI isolate. Despite so far being associated with mild disease in human patients, the cattle H5N1 virus showed superior growth capability and rapid replication kinetics in a panel of human lung cell lines in vitro. In vivo, cattle H5N1 exhibited more intense pathogenicity in mice, with rapid lung pathology and high virus titers in the brain, accompanied by high mortality after challenge via different inoculation routes. Additionally, the cattle H5N1 demonstrated efficient antagonism of overexpressed RIG-I- and MDA5-mediated innate antiviral signaling pathways. In summary, this study demonstrates the profound pathogenicity and suggests a potential innate immune escape mechanism of the H5N1 virus isolated from a dairy cow in Texas.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-93493-5

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Saturday, March 15, 2025

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    The Compensatory Effect of S375F on S371F Is Vital for Maintaining the Infectivity of SARS-CoV-2 Omicron Variants.
    J Med Virol. 2025;97:e70242.
    PubMed         Abstract available

  12. GARCIA-VIDAL C, Teijon-Lumbreras C, Aiello TF, Chumbita M, et al
    COVID-19 Patients Benefitting From Remdesivir for Improved Survival: A Neural Network-Based Approach.
    J Med Virol. 2025;97:e70276.
    PubMed         Abstract available


    JAMA

  13. LAURING AS, Edson C, Surie D, Dawood FS, et al
    Genomic Characterization of RSV in the US by Vaccination Status.
    JAMA. 2025 Mar 10. doi: 10.1001/jama.2025.1225.
    PubMed        


    Lancet

  14. SINGH B, Lipunga GD, Thangavelu P, Dhar S, et al
    A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study.
    Lancet. 2025 Mar 10:S0140-6736(25)00263-6. doi: 10.1016/S0140-6736(25)00263.
    PubMed         Abstract available

  15. WEISS DJ, Dzianach PA, Saddler A, Lubinda J, et al
    Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum and Plasmodium vivax malaria, 2000-22: a spatial and temporal modelling study.
    Lancet. 2025 Mar 5:S0140-6736(25)00038-8. doi: 10.1016/S0140-6736(25)00038.
    PubMed         Abstract available


    Nature

  16. GOETZKE CC, Massoud M, Frischbutter S, Guerra GM, et al
    TGFbeta links EBV to multisystem inflammatory syndrome in children.
    Nature. 2025 Mar 12. doi: 10.1038/s41586-025-08697.
    PubMed         Abstract available

  17. CALLAWAY E
    Four ways COVID changed virology: lessons from the most sequenced virus of all time.
    Nature. 2025;639:293-295.
    PubMed        


  18. Immune molecule links COVID?19 with severe inflammatory disorder in children.
    Nature. 2025 Mar 12. doi: 10.1038/d41586-025-00735.
    PubMed        


    Pol J Radiol

  19. HAJSADEGHI S, Kasaei M, Pouraliakbar H, Jamalkhani S, et al
    Comparing myocardial injury patterns and outcomes in cardiac magnetic resonance imaging between COVID-19- and non-COVID-19-related myocarditis.
    Pol J Radiol. 2025;90:e36-e45.
    PubMed         Abstract available


    Science

  20. WADMAN M
    No sign that vaccine advisers are beholden to industry.
    Science. 2025;387:1131-1132.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, March 15 '25)

 


    Biochemistry (Mosc)

  1. FILIPPOVA TA, Masamrekh RA, Farafonova TE, Khudoklinova YY, et al
    Determination of SARS-CoV-2 Main Protease (M(pro)) Activity Based on Electrooxidation of Tyrosine Residue of a Model Peptide.
    Biochemistry (Mosc). 2025;90:120-131.
    PubMed         Abstract available


    BMC Pediatr

  2. JAYARATNE K, Illangasinghe P, Wanniarachchi S, Hettiarachchi D, et al
    Epidemic profile of COVID-19 child deaths in Sri Lanka: a retrospective nationwide analysis.
    BMC Pediatr. 2025;25:174.
    PubMed         Abstract available


    Cell

  3. XING L, Liu Z, Wang X, Liu Q, et al
    Early fusion intermediate of ACE2-using coronavirus spike acting as an antiviral target.
    Cell. 2025;188:1297-1314.
    PubMed         Abstract available


    J Epidemiol Community Health

  4. COSTE M, Prah JJ
    Applying the health capability profile: an analytical study of leading causes of death in the USA and of pressing public health issues.
    J Epidemiol Community Health. 2025;79:302-310.
    PubMed         Abstract available

  5. AGARWAL G, Keshavarz H, Angeles R, Pirrie M, et al
    SARS-CoV-2 testing, test positivity and vaccination in social housing residents compared with the general population: a retrospective population-based cohort study.
    J Epidemiol Community Health. 2025;79:233-238.
    PubMed         Abstract available

  6. JIN H, Lee WJ, Maupin D, Lee JO, et al
    Within-person relationship between employment insecurity and mental health: a longitudinal analysis of the Understanding America Study.
    J Epidemiol Community Health. 2025;79:265-271.
    PubMed         Abstract available


    J Immunol

  7. GROVENSTEIN P, Bhatnagar N, Kim KH, Pal SS, et al
    Influenza 5xM2e mRNA lipid nanoparticle vaccine confers broad immunity and significantly enhances the efficacy of inactivated split vaccination when coadministered.
    J Immunol. 2025;214:104-114.
    PubMed         Abstract available

  8. QIAO P, Yue C, Peng W, Liu K, et al
    Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2.
    J Immunol. 2025;214:115-129.
    PubMed         Abstract available

  9. WANG M, Liu C, Fan Q, Sun Y, et al
    Rapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies.
    J Immunol. 2025;214:278-289.
    PubMed         Abstract available


    J Infect Dis

  10. VILLALOBOS RODRIGUEZ AP, Wellington Perkins I, Moosavi S, de la Garza A, et al
    Pandemic Preparedness: Analyzing National Plans for Respiratory Pathogen Pandemics in the Americas Region.
    J Infect Dis. 2025;231.
    PubMed         Abstract available

  11. REDONDO-BRAVO L, Zureick K, Voto C, Molina Avendano X, et al
    A Comparative Analysis of Universal and Sentinel Surveillance Data for Coronavirus Disease 2019: Insights From Argentina, Chile, and Mexico (2020-2022).
    J Infect Dis. 2025;231.
    PubMed         Abstract available

  12. RODRIGUEZ A, Couto P, Acevedo A, Herrera BA, et al
    Strengthening the Surveillance and Response to Public Health Events With a One Health Approach: A Perspective From 12 Countries in Latin America and the Caribbean.
    J Infect Dis. 2025;231.
    PubMed         Abstract available


    JAMA

  13. MAIA IS, Kawano-Dourado L, Tramujas L, de Oliveira NE, et al
    High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial.
    JAMA. 2024 Dec 10. doi: 10.1001/jama.2024.26244.
    PubMed         Abstract available


    MMWR Morb Mortal Wkly Rep

  14. ZHU S, Harriman K, Liu C, Kraushaar V, et al
    Human Cases of Highly Pathogenic Avian Influenza A(H5N1) - California, September-December 2024.
    MMWR Morb Mortal Wkly Rep. 2025;74:127-133.
    PubMed         Abstract available


    PLoS Comput Biol

  15. AMARAL AVR, Wolffram D, Moraga P, Bracher J, et al
    Post-processing and weighted combination of infectious disease nowcasts.
    PLoS Comput Biol. 2025;21:e1012836.
    PubMed         Abstract available


    PLoS Med

  16. AHMADI-ABHARI S, Bandosz P, Shipley MJ, Lindbohm JV, et al
    Direct and indirect impacts of the COVID-19 pandemic on life expectancy and person-years of life lost with and without disability: A systematic analysis for 18 European countries, 2020-2022.
    PLoS Med. 2025;22:e1004541.
    PubMed         Abstract available


    PLoS One

  17. ADAMU H, Lawal S, Bawa IA, Sani AM, et al
    Prevalence and pattern of adverse events following COVID-19 vaccination among adult population in Sokoto metropolis, northwest, Nigeria.
    PLoS One. 2025;20:e0277585.
    PubMed         Abstract available

  18. GONCALVES NV, Leal AL, Guimaraes HMMES, Bernardes AC, et al
    The territorialization of Severe Acute Respiratory Syndrome and its socioeconomic, demographic and public health policy risk factors in Belem, state of Para, Eastern Amazon, Brazil: a cross-sectional and ecological study.
    PLoS One. 2025;20:e0318607.
    PubMed         Abstract available

  19. DEGUCHI Y, Iwasaki S, Uesaka Y, Okawa Y, et al
    Remote work and long-term sickness absence due to mental disorder trends among Japanese workers pre/post COVID-19.
    PLoS One. 2025;20:e0319825.
    PubMed         Abstract available

  20. HTET H, Wichaidit W, Chuaychai A, Sottiyotin T, et al
    Perspectives of stakeholders on barriers to COVID-19 protective behaviors adherence and vaccination among Myanmar migrant workers in southern Thailand: A qualitative study.
    PLoS One. 2025;20:e0317714.
    PubMed         Abstract available

  21. MOHRI P, Koyluoglu YO, Seker ME, Sancak SN, et al
    Medical students' perception of paid E-learning.
    PLoS One. 2025;20:e0317340.
    PubMed         Abstract available


    Proc Natl Acad Sci U S A

  22. WANG Q, Xu S, Shen W, Wei Y, et al
    N6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins.
    Proc Natl Acad Sci U S A. 2025;122:e2411554122.
    PubMed         Abstract available


    Vaccine

  23. KRAMMER F
    Next-generation seasonal influenza virus vaccines need a neuraminidase component.
    Vaccine. 2025;54:126994.
    PubMed        

  24. OTIENO NA, Kalani R, Ayugi J, Nyawanda BO, et al
    Seasonal influenza vaccination in Kenya: What determines healthcare Workers' willingness to accept and recommend vaccination?
    Vaccine. 2025;54:126963.
    PubMed         Abstract available


    Virology

  25. OSPINA-JIMENEZ AF, Gomez AP, Rincon-Monroy MA, Perez DR, et al
    A novel reassorted swine H3N2 influenza virus demonstrates an undetected human-to-swine spillover in Latin America and highlights zoonotic risks.
    Virology. 2025;606:110483.
    PubMed         Abstract available

  26. PAWAR SD, Keng SS, Tare DS, Balakrishnan A, et al
    Evidence of novel reassortment in clade 2.3.4.4b avian influenza H5N1 viruses, India, 2024.
    Virology. 2025;606:110482.
    PubMed         Abstract available

Altered #receptor-binding #specificity of #gull-adapted #H13 avian #influenza viruses corresponds to their unique host preferences

Highlights

• H13 HAs exhibit binding specificity for fucosylate α2-3 sialosides.

• The 130-loop and K227 are critical for H13 HA binding specificity.

• Fucosylated α2-3 sialosides are widely distributed in slaty-backed gulls.


Abstract

Avian influenza viruses (AIVs) recognize α2-3 sialosides as receptors. Previous studies showed that the structural diversity within α2-3 sialosides is related to the host specificity of AIVs. H13 AIVs are primarily isolated from gulls, although almost all AIV subtypes have been isolated from ducks, the natural hosts of AIVs. To elucidate the molecular basis of the host specificity of H13 viruses to gulls, the receptor-binding specificity of H13 hemagglutinins (HAs) and the distribution of viral receptors in gulls were investigated. The results revealed that recombinant HA (rHA) of H13 viruses had a binding preference for fucosylated α2-3 sialosides, which were distributed widely in the respiratory tract and intestines of gulls but not in the colon of ducks. Moreover, the receptor-binding specificity of mutant rHAs revealed that amino acids in the 130-loop and at position 227 of H13 HA were critical for the preference for fucosylated α2-3 sialosides. The results of the present study suggest that the binding specificity of H13 HA to fucosylated α2-3 sialosides is a key factor for the host susceptibility of H13 viruses to gulls.

Source: Virology, https://www.sciencedirect.com/science/article/abs/pii/S0042682225000728?via%3Dihub

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Friday, March 14, 2025

Prevalence of #EBV, #HHV6, #HCMV, #HAdV, #SARS-CoV-2, and #Autoantibodies to Type I #Interferon in #Sputum from Myalgic Encephalomyelitis / #CFS Patients

Abstract

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein–Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/422

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {as of March 14 '25}


 

Time Period: March 02 - March 08, 2025

- H5 Detection29 sites (6.2%)

- No Detection438 sites (93.8%)

- No samples in last week152 sites




(...)

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

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An #overview of #influenza #H5 #vaccines

{Summary}

Pandemic influenza remains a significant global health threat, as signalled by the circulation and cross-species transmission of avian influenza A(H5N1) viruses from the clade 2.3.4.4b, including among dairy cattle in the USA since 2024. Although most of the reported human infections from the USA so far1,2 have been mild, the virus can change its profile rapidly. To reduce mortality and morbidity from influenza in humans, vaccines remain the most important intervention.

(...)


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Thursday, March 13, 2025

Direct and indirect #impacts of #COVID19 #pandemic on #life #expectancy and person-years of life lost with & without #disability: A systematic analysis for 18 European countries, 2020–22

Abstract

Background

The direct and indirect impacts of the COVID-19 pandemic on life expectancy (LE) and years of life lost with and without disability remain unclear. Accounting for pre-pandemic trends in morbidity and mortality, we assessed these impacts in 18 European countries, for the years 2020–2022.

Methods and Findings

We used multi-state Markov modeling based on several data sources to track transitions of the population aged 35 or older between eight health states from disease-free, combinations of cardiovascular disease, cognitive impairment, dementia, and disability, through to death. We quantified separately numbers and rates of deaths attributable to COVID-19 from those related to mortality from other causes during 2020–2022, and estimated the proportion of loss of life expectancy and years of life with and without disability that could have been avoided if the pandemic had not occurred. Estimates were disaggregated by COVID-19 versus non-COVID causes of deaths, calendar year, age, sex, disability status, and country. We generated the 95% uncertainty intervals (UIs) using Monte Carlo simulations with 500 iterations. Among the 289 million adult population in the 18 countries, person-years of life lost (PYLL) in millions were 4.7 (95% UI 3.4–6.0) in 2020, 7.1 (95% UI 6.6–7.9) in 2021, and 5.0 (95% UI 4.1–6.2) in 2022, totaling 16.8 (95% UI 12.0–21.8) million. PYLL per capita varied considerably between the 18 countries ranging between 20 and 109 per 1,000 population. About 60% of the total PYLL occurred among persons aged over 80, and 30% in those aged 65–80. If the pandemic were avoided, over half (9.8 million (95% UI 4.7–15.1)) of the 16.8 million PYLL were estimated to have been lived without disability. Of the total PYLL, 11.6–13.2 million were due to registered COVID-19 deaths and 3.6–5.3 million due to non-COVID mortality. Despite a decrease in PYLL attributable to COVID-19 after 2021, PYLL associated with other causes of death continued to increase from 2020 to 2022 in most countries. Lower income countries had higher PYLL per capita as well as a greater proportion of disability-free PYLL during 2020–2022. Similar patterns were observed for life expectancy. In 2021, LE at age 35 (LE-35) declined by up to 2.8 (95% UI 2.3–3.3) years, with over two-thirds being disability-free. With the exception of Sweden, LE-35 in the studied countries did not recover to 2019 levels by 2022.

Conclusions

The considerable loss of life without disability and the rise in premature mortality not directly linked to COVID-19 deaths during 2020–2022 suggest a potential broader, longer-term and partially indirect impact of the pandemic, possibly resulting from disruptions in healthcare delivery and services for non-COVID conditions and unintended consequences of COVID-19 containment measures. These findings highlight a need for better pandemic preparedness in Europe, ideally, as part of a more comprehensive global public health agenda.

Source: PLoS Medicine, https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004541

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#Ukraine - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

Captive birds: 39 chickens, 23 ducks, 17 pheasants, 4 swans, 3 guinea fowls, 3 geese, 2 pigeons, 1 jay, 1 falcon in Kharkiv Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6329

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#Human Cases of Highly Pathogenic Avian #Influenza A(#H5N1) — #California, September–December 2024

Summary

-- What is already known about this topic?

Persons with occupational exposure to highly pathogenic avian influenza (HPAI) A(H5N1) virus–infected dairy cattle are at increased risk for infection.

-- What is added by this report?

During September 30–December 24, 2024, a total of 38 persons received a positive test result for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows. One, a person aged <18 years with an undetermined exposure, was the first pediatric patient detected with influenza A(H5) infection in the United States.

-- What are the implications for public health practice?

Public health agencies should investigate influenza-like illness or conjunctivitis in workers with occupational exposure to animals infected with HPAI A(H5N1) virus. Thorough investigations of all human HPAI A(H5N1) virus infections are necessary to identify potential exposure sources, including monitoring the virus for concerning genetic changes that indicate the potential for person-to-person transmission.


Abstract

Persons who work closely with dairy cows, poultry, or other animals with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) viruses are at increased risk for infection. In September 2024, the California Department of Public Health was notified of the first human case of HPAI A(H5N1) in California through monitoring of workers on farms with infected cows. During September 30–December 24, 2024, a total of 38 persons received positive test results for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows, and one was a child aged <18 years with an undetermined exposure, the first pediatric HPAI A(H5N1) case reported in the United States. All patients had mild illness. The identification of cases associated with occupational exposure to HPAI A(H5N1) viruses on dairy farms highlights the continued risk for persons who work with infected animals. The pediatric case was identified through routine surveillance. Given recent increases in the prevalence of HPAI A(H5N1) viruses among some animal populations, public health agencies should continue to investigate cases of HPAI A(H5N1) in humans as part of control measures, pandemic preparedness, to identify concerning genetic changes, and to prevent and detect potential human-to-human transmission of the virus. To date, no human-to-human transmission of HPAI A(H5N1) virus has been identified in the United States.

Source: US Centers for Disease Control and Prevention (MMWR), http://dx.doi.org/10.15585/mmwr.mm7408a1

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The Novel #H10N3 Avian #Influenza Virus Triggers Lethal #Cytokine #Storm by Activating Multiple Forms of Programmed Cell Death in Mammalian #Lungs

Abstract

The novel H10N3 avian influenza virus (AIV) has infected four individuals since 2021 and caused severe respiratory damage, posing a significant threat to public health. However, its pathogenic mechanisms remain poorly understood. Our findings revealed that H10N3 infection induces severe lung damage and causes death in mice, even at low doses. The elevated levels of multiple pro-inflammatory factors in the bronchoalveolar lavage fluid were significantly increased during infection, displaying hallmarks of a cytokine storm. Transcriptome sequencing further revealed systematic activation of inflammation-related pathways, predicting that viral infection induces multiple forms of programmed cell death, including apoptosis, pyroptosis, and necroptosis. Protein-level validation showed that the activation of key cell death markers, including Caspase-3, GSDMD, and MLKL, significantly increased as the infection progressed, with their dynamic changes correlating strongly with the expression pattern of viral proteins. This study elucidates the central role of the synergistic effect between the cytokine storm and multiple cell death pathways in H10N3 pathogenesis. These findings not only advance our understanding of the pathogenic mechanisms of AIVs but also provide a critical theoretical basis for the development of targeted therapeutic strategies.

Source: International Journal of Molecular Sciences, https://www.mdpi.com/1422-0067/26/5/1977

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Antigenicity and genetic #properties of an #Eurasian #avian-like #H1N1 swine #influenza virus in #Jiangsu Province, #China

Highlights

• Scientific questionCross-species transmission of influenza A viruses from swine to humans occurs occasionally because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors. In 2011, the first human case of swine influenza virus infection in the mainland of China was detected in Jiangsu Province. Subsequently, the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIV) had sporadically crossed the host barrier and infected humans, raising public concern for its pandemic potential.

• Evidence before this studyA/Jiangsu/1/2011 (H1N1v) was first discovered in 2011 and belongs to the G1 genotype. The G4 and G5 genotypes that appeared successively in 2013 are recombinant H1N1 swine influenza viruses. The EAH1N1 SIVs from 2016 to the present are dominated by the G4 genotype, with hemagglutination (HA) and neuraminidase (NA) genes derived from the EAH1N1 SIVs, non-structural protein (NS) genes derived from the triple-origin reassortant swine influenza viruses, and the rest of the internal genes from influenza A (H1N1) pdm09 virus.

• New findingsThis study investigated a case of the EAH1N1 SIV infection in a child. This is the first case of the EAH1N1 SIV genotype G4 infection in a child in Jiangsu Province. This virus maintained the genetic properties of the EAH1N1 SIV but differed significantly in HA protein antigens.

• Significance of the studyThis new human case of the EAH1N1 SIV infection indicates the pandemic potential of avian influenza viruses.


Abstract

Pigs are vital genetic mixing vessels for human and avian influenza viruses because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors. Cross-species transmission of influenza A viruses from swine to humans occurs occasionally. The first case of human infection with the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIVs) genotype G4 was detected in Jiangsu Province, China, in February 2023, and backtracking epidemiological investigations did not reveal a clear source of the infection. The hemagglutination (HA) and neuraminidase (NA) amino acid variant sites, antiviral drug susceptibility, and antigenic variation of the isolated A/Jiangsu/27271/2023 (JS/27271/23) virus were analyzed, and we evaluated the protective effect of sera collected from occupationally exposed populations in 2024 against the virus. Compared with the vaccine strain, the nucleotide sequence similarities of JS/27271/23 HA and NA were 96.5 % and 95.2 %, respectively. JS/27271/23 was sensitive to polymerase inhibitors (favipiravir and baloxavir), and the antigenicity of its HA protein was 8-fold different from that of the vaccine strain. The percentage of occupationally exposed population with antibody titers of ≥ 40 against A/Hunan/42443/2015 (HN/42443/15) and A/Jiangsu/1/2011 (JS/1/11) were 7.25 % and 2.25 %, respectively, and the geometric mean titers (GMT) were 6.24 and 5.34, respectively. Out of 400 serum samples examined, none had antibody titers of ≥ 40 against JS/27271/23. This suggests that low serum levels of antibodies to EAH1N1 SIVs in occupationally exposed populations may not provide adequate protection because of significant differences in amino acid sites and antigenicity between this virus and the current vaccine strain of EAH1N1 SIVs. There is no evidence of human-to-human transmission of EAH1N1 SIVs. Therefore, surveillance for EAH1N1 SIVs and the development of new vaccine strains are required.

Source: Biosafety and Health, https://www.sciencedirect.com/science/article/pii/S2590053624001381?via%3Dihub

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