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Frontiers in Public Health 2020Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Constantly evolving and crossing species barrier, the emergence... (Review)
Review
Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Constantly evolving and crossing species barrier, the emergence of novel zoonotic pathogens is one of the greatest challenges to global health security. During the last decade, considerable attention has been paid to influenza virus infections in dogs, as two canine H3N8 and H3N2 subtypes caused several outbreaks through the United States and Southern Asia, becoming endemic. Cats, even though less documented in the literature, still appear to be susceptible to many avian influenza infections. While influenza epidemics pose a threat to canine and feline health, the risks to humans are largely unknown. Here, we review most recent knowledge of the epidemiology of influenza A viruses in dogs and cats, existing evidences for the abilities of these species to host, sustain intraspecific transmission, and generate novel flu A lineages through genomic reassortment. Such enhanced understanding suggests a need to reinforce surveillance of the role played by companion animals-human interface, in light of the "One Health" concept and the potential emergence of novel zoonotic viruses.
Topics: Animals; Asia; Cat Diseases; Cats; Dog Diseases; Dogs; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H3N8 Subtype; Influenza A virus; Influenza, Human; United States
PubMed: 32266198
DOI: 10.3389/fpubh.2020.00083 -
Scientific Reports May 2021Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant...
Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Aprotinin has been previously reported to show inhibitory effects on a few influenza A virus (IAV) subtypes (e.g., seasonal H1N1 and H3N2). However, because there were no reports of its inhibitory effects on the other types of influenza viruses, we investigated the inhibitory effects of aprotinin in vitro on a wide range of influenza viruses, including avian and oseltamivir-resistant influenza virus strains. Our cell-based assay showed that aprotinin had inhibitory effects on seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5, and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently circulating influenza B virus. We have also confirmed its activity in mice infected with a lethal dose of influenza virus, showing a significant increase in survival rate. Our findings suggest that aprotinin has the capacity to inhibit a wide range of influenza virus subtypes and should be considered for development as a therapeutic agent against influenza.
Topics: Animals; Antiviral Agents; Aprotinin; Cell Line; Dogs; Drug Evaluation, Preclinical; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N2 Subtype; Influenza A Virus, H9N2 Subtype; Influenza B virus; Madin Darby Canine Kidney Cells; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections; Serine Proteinase Inhibitors
PubMed: 33941825
DOI: 10.1038/s41598-021-88886-1 -
Frontiers in Immunology 2023Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required....
INTRODUCTION
Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate immune reactions induced by IAV are based on quantitative/functional methods and anatomical exploration is most often non-existent. We aimed to study pulmonary damage and macrophage recruitment using two-photon excitation microscopy (TPEM) after IAV infection.
METHODS
We infected C57BL/6 CD11cYFP mice with A/Puerto Ricco/8/34 H1N1. We performed immune cell analysis, including flow cytometry, cytokine concentration assays, and TPEM observations after staining with anti-F4/80 antibody coupled to BV421. We adapted live lung slice (LLS) method for intravital microscopy to analyze cell motility.
RESULTS
TPEM provided complementary data to flow cytometry and cytokine assays by allowing observation of bronchial epithelium lesions and spreading of local infection. Addition of F4/80-BV421 staining allowed us to precisely determine timing of recruitment and pulmonary migration of macrophages. LLS preserved cellular viability, allowing us to observe acceleration of macrophage motility.
CONCLUSION
After IAV infection, we were able to explore structural consequences and successive waves of innate immune cell recruitment. By combining microscopy, flow cytometry and chemokine measurements, we describe novel and precise scenario of innate immune response against IAV.
Topics: Animals; Mice; Humans; Mice, Inbred C57BL; Alphainfluenzavirus; Disease Models, Animal; Influenza A Virus, H1N1 Subtype; Influenza A virus; Immunity, Innate; Influenza, Human; Microscopy, Fluorescence; Cytokines
PubMed: 37649477
DOI: 10.3389/fimmu.2023.1241323 -
PLoS Pathogens Apr 2020The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose...
The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.
Topics: Animals; Communicable Diseases, Emerging; Dog Diseases; Dogs; Ferrets; Guinea Pigs; Humans; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H3N8 Subtype; Influenza A virus; Influenza, Human; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; United States; Zoonoses
PubMed: 32287326
DOI: 10.1371/journal.ppat.1008409 -
Nature Communications Nov 2022Improved vaccines and antiviral agents that provide better, broader protection against seasonal and emerging influenza viruses are needed. The viral surface glycoprotein...
Improved vaccines and antiviral agents that provide better, broader protection against seasonal and emerging influenza viruses are needed. The viral surface glycoprotein hemagglutinin (HA) is a primary target for the development of universal influenza vaccines and therapeutic antibodies. The other major surface antigen, neuraminidase (NA), has been less well studied as a potential target and fewer broadly reactive anti-NA antibodies have been identified. In this study, we isolate three human monoclonal antibodies that recognize NA from A/H1N1 subtypes, and find that one of them, clone DA03E17, binds to the NA of A/H3N2, A/H5N1, A/H7N9, B/Ancestral-lineage, B/Yamagata-lineage, and B/Victoria-lineage viruses. DA03E17 inhibits the neuraminidase activity by direct binding to the enzyme active site, and provides in vitro and in vivo protection against infection with several types of influenza virus. This clone could, therefore, be useful as a broadly protective therapeutic agent. Moreover, the neutralizing epitope of DA03E17 could be useful in the development of an NA-based universal influenza vaccine.
Topics: Humans; Influenza, Human; Neuraminidase; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Herpesvirus 1, Cercopithecine; Influenza A Virus, H5N1 Subtype; Antibodies, Monoclonal; Influenza A Virus, H7N9 Subtype; Orthomyxoviridae Infections; Antibodies, Viral; Influenza Vaccines
PubMed: 36329075
DOI: 10.1038/s41467-022-34521-0 -
Biomedicine & Pharmacotherapy =... Feb 2022Epimedium koreanum Nakai (EKN) is a popular plant in Korean and Chinese medicine for treating a variety of ailments. The aqueous extract of EKN has a significant...
Epimedium koreanum Nakai (EKN) is a popular plant in Korean and Chinese medicine for treating a variety of ailments. The aqueous extract of EKN has a significant inhibitory impact on influenza A virus (IAV) infection by directly blocking viral attachment and having a virucidal effect, according to this study. Using fluorescent microscopy and fluorescence-activated cell sorting (FACS) with a green fluorescent protein (GFP)-tagged Influenza A/PR/8/34 virus, we examined the effect of EKN on viral infection. By viral infection, EKN strongly suppresses GFP expression, and at a dosage of 100 µg/mL, EKN decreased GFP expression by up to 90% of the untreated infected control. Immunofluorescence and Western blot analyses against influenza viral proteins revealed that EKN decreased influenza viral protein expression in a dose-dependent manner. EKN inhibited the H1N1 influenza virus's hemagglutinin (HA) and neuraminidase (NA), preventing viral attachment to cells. Furthermore, EKN had a virucidal impact and inhibited the cytopathic effects of H1N1, H3N2 and influenza B virus infection. Finally, our findings show that EKN has the potential to be developed as a natural viral inhibitor against influenza virus infection.
Topics: Animals; Antiviral Agents; Epimedium; Hemagglutinins; Humans; Alphainfluenzavirus; Mice; Neuraminidase; Plant Extracts; Viral Proteins; Virus Attachment
PubMed: 34965505
DOI: 10.1016/j.biopha.2021.112581 -
Expert Review of Anti-infective Therapy May 2010Molecular-based techniques for detecting influenza viruses have become an integral component of human and animal surveillance programs in the last two decades. The... (Review)
Review
Molecular-based techniques for detecting influenza viruses have become an integral component of human and animal surveillance programs in the last two decades. The recent pandemic of the swine-origin influenza A virus (H1N1) and the continuing circulation of highly pathogenic avian influenza A virus (H5N1) further stress the need for rapid and accurate identification and subtyping of influenza viruses for surveillance, outbreak management, diagnosis and treatment. There has been remarkable progress on the detection and molecular characterization of influenza virus infections in clinical, mammalian, domestic poultry and wild bird samples in recent years. The application of these techniques, including reverse transcriptase-PCR, real-time PCR, microarrays and other nucleic acid sequencing-based amplifications, have greatly enhanced the capability for surveillance and characterization of influenza viruses.
Topics: Animals; Bird Diseases; Birds; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A virus; Influenza, Human; Molecular Diagnostic Techniques; Orthomyxoviridae Infections; Polymerase Chain Reaction; Population Surveillance; Poultry Diseases; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 20455681
DOI: 10.1586/eri.10.24 -
Virology Journal Aug 2023Influenza A virus (IAV) is endemic in pigs globally and co-circulation of genetically and antigenically diverse virus lineages of subtypes H1N1, H1N2 and H3N2 is a...
BACKGROUND
Influenza A virus (IAV) is endemic in pigs globally and co-circulation of genetically and antigenically diverse virus lineages of subtypes H1N1, H1N2 and H3N2 is a challenge for the development of effective vaccines. Virosomes are virus-like particles that mimic virus infection and have proven to be a successful vaccine platform against several animal and human viruses.
METHODS
This study evaluated the immunogenicity of a virosome-based influenza vaccine containing the surface glycoproteins of H1N1 pandemic, H1N2 and H3N2 in pigs.
RESULTS
A robust humoral and cellular immune response was induced against the three IAV subtypes in pigs after two vaccine doses. The influenza virosome vaccine elicited hemagglutinin-specific antibodies and virus-neutralizing activity. Furthermore, it induced a significant maturation of macrophages, and proliferation of B lymphocytes, effector and central memory CD4 and CD8 T cells, and CD8 T lymphocytes producing interferon-γ. Also, the vaccine demonstrated potential to confer long-lasting immunity until the market age of pigs and proved to be safe and non-cytotoxic to pigs.
CONCLUSIONS
This virosome platform allows flexibility to adjust the vaccine content to reflect the diversity of circulating IAVs in swine in Brazil. The vaccination of pigs may reduce the impact of the disease on swine production and the risk of swine-to-human transmission.
Topics: Humans; Animals; Swine; Influenza Vaccines; Influenza, Human; Vaccines, Combined; Immunity, Humoral; CD8-Positive T-Lymphocytes; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Virosomes; Influenza A virus
PubMed: 37587490
DOI: 10.1186/s12985-023-02153-5 -
International Journal of Environmental... Apr 2020H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact...
H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000-2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.
Topics: Environment; Humans; Influenza A Virus, H1N1 Subtype; Influenza A virus; Influenza, Human; Mutation; Phylogeny
PubMed: 32365515
DOI: 10.3390/ijerph17093092 -
Viruses Sep 2019With the emergence of drug-resistant strains of influenza A viruses (IAV), new antivirals are needed to supplement the existing counter measures against IAV infection....
With the emergence of drug-resistant strains of influenza A viruses (IAV), new antivirals are needed to supplement the existing counter measures against IAV infection. We have previously shown that brevilin A, a sesquiterpene lactone isolated from , suppresses the infection of influenza A/PR/8/34 (H1N1) in vitro. Here, we further investigate the antiviral activity and mode of action of brevilin A against different IAV subtypes. Brevilin A inhibited the replication of influenza A H1N1, H3N2, and H9N2 viruses in vitro. The suppression effect of brevilin A was observed as early as 4-8 hours post infection (hpi). Furthermore, we determined that brevilin A inhibited viral replication in three aspects, including viral RNA (vRNA) synthesis, expression of viral mRNA, and protein encoded from the M and NS segments, and nuclear export of viral ribonucleoproteins (vRNPs). The anti-IAV activity of brevilin A was further confirmed in mice. A delayed time-to-death with 50% surviving up to 14 days post infection was obtained with brevilin A (at a dose of 25 mg/kg) treated animals compared to the control cohorts. Together, these results are encouraging for the exploration of sesquiterpene lactones with similar structure to brevilin A as potential anti-influenza therapies.
Topics: Animals; Antiviral Agents; Crotonates; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H9N2 Subtype; Influenza, Human; Mice; Mice, Inbred BALB C; Sesquiterpenes; Virus Replication
PubMed: 31500389
DOI: 10.3390/v11090835