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BioRxiv : the Preprint Server For... May 2024H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human...
H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.
PubMed: 38826368
DOI: 10.1101/2024.05.23.595634 -
MedRxiv : the Preprint Server For... May 2024Spillover of highly pathogenic avian H5N1 into the cattle population poses a risk to humans through the close contact with farm workers. High viral loads of influenza...
Spillover of highly pathogenic avian H5N1 into the cattle population poses a risk to humans through the close contact with farm workers. High viral loads of influenza viruses in the unpasteurized milk of infected lactating cows has the potential to contaminate equipment within milking parlors and create fomites for transmission to dairy workers. Cattle H5N1 and human 2009 H1N1 pandemic influenza viruses were found to remain infectious on surfaces commonly found in milking equipment materials for a few hours. The data presented here provide a compelling case for the risk of contaminated surfaces generated during milking to facilitate transmission of H5N1 from cattle-to-cattle and to dairy farm workers.
PubMed: 38826283
DOI: 10.1101/2024.05.22.24307745 -
The Science of the Total Environment Sep 2024Despite its popularity for water activities, such as swimming, surfing, fishing, and rafting, inland and coastal bathing areas occasionally experience outbreaks of... (Review)
Review
Despite its popularity for water activities, such as swimming, surfing, fishing, and rafting, inland and coastal bathing areas occasionally experience outbreaks of highly pathogenic avian influenza virus (HPAI), including A(H5N1) clade 2.3.4.4b. Asymptomatic infections and symptomatic outbreaks often impact many aquatic birds, which increase chances of spill-over events to mammals and pose concerns for public health. This review examined the existing literature to assess avian influenza virus (AIV) transmission risks to beachgoers and the general population. A comprehensive understanding of factors governing such crossing of the AIV host range is currently lacking. There is limited knowledge on key factors affecting risk, such as species-specific interactions with host cells (including binding, entry, and replication via viral proteins hemagglutinin, neuraminidase, nucleoprotein, and polymerase basic protein 2), overcoming host restrictions, and innate immune response. AIV efficiently transmits between birds and to some extent between marine scavenger mammals in aquatic environments via consumption of infected birds. However, the current literature lacks evidence of zoonotic AIV transmission via contact with the aquatic environment or consumption of contaminated water. The zoonotic transmission risk of the circulating A(H5N1) clade 2.3.4.4b virus to the general population and beachgoers is currently low. Nevertheless, it is recommended to avoid direct contact with sick or dead birds and to refrain from bathing in locations where mass bird mortalities are reported. Increasing reports of AIVs spilling over to non-human mammals have raised valid concerns about possible virus mutations that lead to crossing the species barrier and subsequent risk of human infections and outbreaks.
Topics: Humans; Influenza in Birds; Animals; Influenza, Human; Influenza A Virus, H5N1 Subtype; Disease Outbreaks; Birds; Environmental Monitoring; Bathing Beaches; One Health
PubMed: 38825193
DOI: 10.1016/j.scitotenv.2024.173692 -
BMC Infectious Diseases Jun 2024Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally...
BACKGROUND
Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans.
METHODS
Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software.
RESULTS
RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP).
CONCLUSIONS
The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.
Topics: Influenza A Virus, H1N1 Subtype; China; Humans; Male; Phylogeny; Animals; Influenza, Human; Dogs; Madin Darby Canine Kidney Cells; Child; Swine; Whole Genome Sequencing; Orthomyxoviridae Infections; Genome, Viral
PubMed: 38824508
DOI: 10.1186/s12879-024-09441-7 -
Medical Science Monitor : International... Jun 2024Highly pathogenic avian influenza (HPAI) virus subtypes have been increasingly identified in poultry and wild birds since 2021. Between 2020-2023, 26 countries have...
Highly pathogenic avian influenza (HPAI) virus subtypes have been increasingly identified in poultry and wild birds since 2021. Between 2020-2023, 26 countries have reported that the H5N1 virus had infected more than 48 mammalian species. On 1 April 2024, a public health alert was issued in Texas when the first confirmed case of human infection with the H5N1 influenza virus was reported in a dairy worker. Cases of H5N1, clade 2.3.4.4b in dairy cows have been reported in several states in the US but were unexpected, even though H5N1 was previously identified in mammalian species, including cats, dogs, bears, foxes, tigers, coyotes, goats, and seals. On 29 April 2024, almost one month after the first reported cases of H5N1 infection in dairy cows, measures were to be implemented by the US Department of Agriculture (USDA) to prevent the progression of H5N1 viral transmission. This editorial summarizes what is currently known about the epidemiology, transmission, and surveillance of the HPAI virus of the H5N1 subtype in birds, mammals, and dairy cows, and why there are concerns regarding transmission to humans.
Topics: Animals; Cattle; Influenza A Virus, H5N1 Subtype; Humans; Influenza in Birds; Influenza, Human; Orthomyxoviridae Infections; Birds; Mammals; Dairying
PubMed: 38822579
DOI: 10.12659/MSM.945315 -
BMC Genomics Jun 2024Several single nucleotide polymorphism (SNP) pipelines exist, each offering its own advantages. Among them and described here is vSNP that has been developed over the...
BACKGROUND
Several single nucleotide polymorphism (SNP) pipelines exist, each offering its own advantages. Among them and described here is vSNP that has been developed over the past decade and is specifically tailored to meet the needs of diagnostic laboratories. Laboratories that aim to provide rapid whole genome sequencing results during outbreak investigations face unique challenges. vSNP addresses these challenges by enabling users to verify and validate sequence accuracy with ease- having utility across various pathogens, being fully auditable, and presenting results that are easy to interpret and can be comprehended by individuals with diverse backgrounds.
RESULTS
vSNP has proven effective for real-time phylogenetic analysis of disease outbreaks and eradication efforts, including bovine tuberculosis, brucellosis, virulent Newcastle disease, SARS-CoV-2, African swine fever, and highly pathogenic avian influenza. The pipeline produces easy-to-read SNP matrices, sorted for convenience, as well as corresponding phylogenetic trees, making the output easily understandable. Essential data for verifying SNPs is included in the output, and the process has been divided into two steps for ease of use and faster processing times. vSNP requires minimal computational resources to run and can be run in a wide range of environments. Several utilities have been developed to make analysis more accessible for subject matter experts who may not have computational expertise.
CONCLUSION
The vSNP pipeline integrates seamlessly into a diagnostic workflow and meets the criteria for quality control accreditation programs, such as 17025 by the International Organization for Standardization. Its versatility and robustness make it suitable for use with a diverse range of organisms, providing detailed, reproducible, and transparent results, making it a valuable tool in various applications, including phylogenetic analysis performed in real time.
Topics: Polymorphism, Single Nucleotide; Phylogeny; Whole Genome Sequencing; Software; Animals; Humans; Computational Biology
PubMed: 38822271
DOI: 10.1186/s12864-024-10437-5 -
Lancet Regional Health. Americas Jul 2024
PubMed: 38818112
DOI: 10.1016/j.lana.2024.100785 -
MMWR. Morbidity and Mortality Weekly... May 2024
Topics: Humans; Animals; United States; Influenza, Human; Cattle; Disease Outbreaks; Influenza A Virus, H5N1 Subtype; Cattle Diseases; Female; Male
PubMed: 38814843
DOI: 10.15585/mmwr.mm7321e1 -
Frontiers in Veterinary Science 2024Recently, herpesvirus of turkeys (HVT), which was initially employed as a vaccine against Marek's disease (MD), has been shown to be a highly effective viral vector for...
Simultaneous construction strategy using two types of fluorescent markers for HVT vector vaccine against infectious bursal disease and H9N2 avian influenza virus by NHEJ-CRISPR/Cas9.
Recently, herpesvirus of turkeys (HVT), which was initially employed as a vaccine against Marek's disease (MD), has been shown to be a highly effective viral vector for producing recombinant vaccines that can simultaneously express the protective antigens of multiple poultry diseases. Prior to the development of commercial HVT-vectored dual-insert vaccines, the majority of HVT-vectored vaccines in use only contained a single foreign gene and were often generated using time-consuming and inefficient traditional recombination methods. The development of multivalent HVT-vectored vaccines that induce simultaneous protection against several avian diseases is of great value. In particular, efficacy interference between individual recombinant HVT vaccines can be avoided. Herein, we demonstrated the use of CRISPR/Cas9 gene editing technology for the insertion of an IBDV (G2d) VP2 expression cassette into the UL45/46 region of the recombinant rHVT-HA viral genome to generate the dual insert rHVT-VP2-HA recombinant vaccine. The efficacy of this recombinant virus was also evaluated in specific pathogen-free (SPF) chickens. PCR and sequencing results showed that the recombinant virus rHVT-VP2-HA was successfully constructed. Vaccination with rHVT-VP2-HA produced high levels of specific antibodies against IBDV (G2d) and H9N2/Y280. rHVT-VP2-HA can provide 100% protection against challenges with IBDV (G2d) and H9N2/Y280. These results demonstrate that rHVT-VP2-HA is a safe and highly efficacious vaccine for the simultaneous control of IBDV (G2d) and H9N2/Y280.
PubMed: 38812565
DOI: 10.3389/fvets.2024.1385958 -
Frontiers in Bioscience (Landmark... May 2024To investigate the immune responses and protection ability of ultraviolet light (UV)-inactivated recombinant vesicular stomatitis (rVSV)-based vectors that expressed a...
BACKGROUND
To investigate the immune responses and protection ability of ultraviolet light (UV)-inactivated recombinant vesicular stomatitis (rVSV)-based vectors that expressed a fusion protein consisting of four copies of the influenza matrix 2 protein ectodomain (tM2e) and the Dendritic Cell (DC)-targeting domain of the Ebola Glycoprotein (EΔM), (rVSV-EΔM-tM2e).
METHOD
In our previous study, we demonstrated the effectiveness of rVSV-EΔM-tM2e to induce robust immune responses against influenza M2e and protect against lethal challenges from H1N1 and H3N2 strains. Here, we used UV to inactivate rVSV-EΔM-tM2e and tested its immunogenicity and protection in BALB/c mice from a mouse-adapted H1N1 influenza challenge. Using Enzyme-Linked Immunosorbent Assay (ELISA) and Antibody-Dependent Cellular Cytotoxicity (ADCC), the influenza anti-M2e immune responses specific to human, avian and swine influenza strains induced were characterized. Likewise, the specificity of the anti-M2e immune responses induced in recognizing M2e antigen on the surface of the cell was investigated using Fluorescence-Activated Cell Sorting (FACS) analysis.
RESULTS
Like the live attenuated rVSV-EΔM-tM2e, the UV-inactivated rVSV-EΔM-tM2e was highly immunogenic against different influenza M2e from strains of different hosts, including human, swine, and avian, and protected against influenza H1N1 challenge in mice. The FACS analysis demonstrated that the induced immune responses can recognize influenza M2 antigens from human, swine and avian influenza strains. Moreover, the rVSV-EΔM-tM2e also induced ADCC activity against influenza M2e from different host strains.
CONCLUSIONS
These findings suggest that UV-inactivated rVSV-EΔM-tM2e could be used as an inactivated vaccine against influenza viruses.
Topics: Animals; Influenza Vaccines; Influenza A Virus, H1N1 Subtype; Ultraviolet Rays; Mice, Inbred BALB C; Orthomyxoviridae Infections; Female; Mice; Humans; Viral Matrix Proteins; Vesiculovirus; Vaccines, Inactivated
PubMed: 38812326
DOI: 10.31083/j.fbl2905195