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Cold Spring Harbor Perspectives in... Oct 2021Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates... (Review)
Review
Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates as receptors but have limited affinity for them, and, as a consequence, virus attachment to cells requires their interaction with several virus HAs. Receptor-bound virus is transferred into endosomes where membrane fusion by HAs is activated at pH between 5 and 6.5, depending on the strain of virus. Fusion activity requires extensive rearrangements in HA conformation that include extrusion of a buried "fusion peptide" to connect with the endosomal membrane, form a bridge to the virus membrane, and eventually bring both membranes close together. In this review, we give an overview of the structures of the 16 genetically and antigenically distinct subtypes of influenza A HA in relation to these two functions in virus replication and in relation to recognition of HA by antibodies that neutralize infection.
Topics: Hemagglutinins; Humans; Hydrogen-Ion Concentration; Membrane Fusion; Orthomyxoviridae
PubMed: 32513673
DOI: 10.1101/cshperspect.a038638 -
Viruses Jan 2011In their recent publication, Rossman et al. describe how the inherent budding capability of its M2 protein allows influenza A virus to bypass recruitment of the cellular...
In their recent publication, Rossman et al. describe how the inherent budding capability of its M2 protein allows influenza A virus to bypass recruitment of the cellular ESCRT machinery enlisted by several other enveloped RNA and DNA viruses, including HIV, Ebola, rabies, herpes simplex type 1 and hepatitis B. Studies from the same laboratory and other laboratories indicate that budding of plasmid-derived virus-like particles can be mediated by the influenza virus hemagglutinin and neuraminidase proteins in the absence of M2. These events are also independent of canonical ESCRT components. Understanding how intrinsic properties of these influenza virus proteins permit ESCRT-independent budding expands our understanding of the budding process itself.
Topics: Cell Membrane; Endosomal Sorting Complexes Required for Transport; Hemagglutinins; Influenza A virus; Neuraminidase; Viral Matrix Proteins; Virus Release
PubMed: 21666754
DOI: 10.3390/v3010026 -
Toxins Jun 2017Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by and other clostridia. The 150 kDa neurotoxin is produced in...
Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs) to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH), and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC), but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs) which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.
Topics: Botulinum Toxins; Clostridium botulinum; Hemagglutinins; Multigene Family; Open Reading Frames
PubMed: 28617306
DOI: 10.3390/toxins9060193 -
Biochemistry. Biokhimiia Jul 2015Wild ducks serve as the primary host for numerous and various influenza type A viruses. Occasionally, viruses from this reservoir can be transferred to other host... (Review)
Review
Wild ducks serve as the primary host for numerous and various influenza type A viruses. Occasionally, viruses from this reservoir can be transferred to other host species and cause outbreaks of influenza in fowl, swine, and horses, as well as result in novel human pandemics. Cellular tropism and range of susceptible host species are determined by interaction between virus and receptor molecules on cells. Here we discuss modern data regarding molecular features underlying interactions of influenza viruses with cellular receptors as well as a role for receptor specificity in interspecies transmission. By analyzing the earliest available pandemic influenza viruses (1918, 1957, 1968, 2009), we found that hemagglutinin reconfigured to recognize 2-6 sialic acid-containing receptors in the human upper airway tract together with altered enzymatic activity of neuraminidase necessary for maintaining functional balance with hemagglutinin are responsible for effective spread of influenza viruses in human populations. Resistance to low pH also contributes to this. Thus, a combination of such parameters makes it possible that influenza viruses give rise to novel pandemics.
Topics: Animals; Birds; Disease Transmission, Infectious; Hemagglutinins; Humans; Influenza A Virus, H1N1 Subtype; Influenza A virus; Influenza in Birds; Influenza, Human; Neuraminidase; Viral Proteins
PubMed: 26542001
DOI: 10.1134/S000629791507007X -
Veterinaria Italiana Sep 2019Each year millions of people are infected by influenza viruses, and this causes a substantial economic and health burden on our society. Influenza epidemics and... (Review)
Review
Each year millions of people are infected by influenza viruses, and this causes a substantial economic and health burden on our society. Influenza epidemics and pandemics are attributable to the ongoing evolution of influenza viruses through antigenic drift and shift, respectively. One of the reasons for the continuous circulation of influenza viruses in the human population is the incomplete protection conferred by currently available seasonal influenza vaccines against possible arising drifted or shifted influenza strains. Recently, tremendous efforts have been focused on the development of a more effective broadly reactive or universal influenza vaccine. The main objective of underdevelopment vaccines is to protect the human population not only from currently circulating virus strains but also from possible future variants without the need for their continuous update. Different approaches have been developed to reach this goal and elicit an effective and cross-protective immune response. Among these, consensus-based prophylactic approaches to effectively prevent influenza infections are the major focus of this review.
Topics: Animals; Hemagglutinins; Humans; Influenza, Human; Orthomyxoviridae; Orthomyxoviridae Infections
PubMed: 31599544
DOI: 10.12834/VetIt.1944.10352.1 -
BMC Research Notes Jun 2019Urinary tract infection (UTI) is one of the most frequent disease encounters in pregnant mothers, and the most drug resistant, biofilm and hemagglutinin producer...
OBJECTIVE
Urinary tract infection (UTI) is one of the most frequent disease encounters in pregnant mothers, and the most drug resistant, biofilm and hemagglutinin producer Uropathogenic Escherichia coli (UPEC) is the major etiologic agent. Therefore, the aim of this study was to assess the association between the antimicrobial resistance, and biofilm and hemagglutinin production of Uropathogenic Escherichia coli.
RESULTS
UTI among the study participants was 27.3%; and UPEC was found the major etiologic agent followed by coagulase negative staphylococcus. Risk factors, previous history of catheterization and previous history of UTI were found significantly associated with UTI, recurrent UTI, drug resistance and biofilm formation. Of the tested antibiotics, nitrofurantoin was the most effective drug for UPEC. Nearly 100% of the biofilm producers were resistant to norfloxacin, cotrimoxazole, and gentamicin.
Topics: Adolescent; Adult; Biofilms; Drug Resistance, Bacterial; Female; Hemagglutinins; Humans; Logistic Models; Multivariate Analysis; Uropathogenic Escherichia coli; Young Adult
PubMed: 31234908
DOI: 10.1186/s13104-019-4382-1 -
Influenza and Other Respiratory Viruses Mar 2024Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but... (Review)
Review
Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but also the economy. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies is currently underway. Promising approaches include targeting the highly conserved epitopes of haemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e) and internal proteins of the influenza virus. The identification and characterization of broadly neutralizing antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.
Topics: Humans; Influenza Vaccines; Influenza, Human; Antibodies, Viral; Orthomyxoviridae; Orthomyxoviridae Infections; Hemagglutinins; Viral Proteins; Hemagglutinin Glycoproteins, Influenza Virus
PubMed: 38513364
DOI: 10.1111/irv.13276 -
Viruses Apr 2022Swine influenza (SI) is a major respiratory disease of swine; SI is due to the influenza A virus of swine (IAV-S), a highly contagious virus with zoonotic potential. The... (Review)
Review
Swine influenza (SI) is a major respiratory disease of swine; SI is due to the influenza A virus of swine (IAV-S), a highly contagious virus with zoonotic potential. The intensity of IAV-S surveillance varies among countries because it is not a reportable disease and causes limited mortality in swine. Although Asia accounts for half of all pig production worldwide, SI is not well managed in those countries. Rigorously managing SI on pig farms could markedly reduce the economic losses, the likelihood of novel reassortants among IAV-S, and the zoonotic IAV-S infections in humans. Vaccination of pigs is a key control measure for SI, but its efficacy relies on the optimal antigenic matching of vaccine strains with the viral strains circulating in the field. Here, we phylogenetically reviewed the genetic diversity of the hemagglutinin gene among IAVs-S that have circulated in Asia during the last decade. This analysis revealed the existence of country-specific clades in both the H1 and H3 subtypes and cross-border transmission of IAVs-S. Our findings underscore the importance of choosing vaccine antigens for each geographic region according to both genetic and antigenic analyses of the circulating IAV-S to effectively manage SI in Asia.
Topics: Animals; Genetic Variation; Hemagglutinins; Humans; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza, Human; Orthomyxoviridae Infections; Phylogeny; Swine; Swine Diseases
PubMed: 35458477
DOI: 10.3390/v14040747 -
Biophysical Journal Apr 2015The clusters of the influenza envelope protein, hemagglutinin, within the plasma membrane are hypothesized to be enriched with cholesterol and sphingolipids. Here, we...
The clusters of the influenza envelope protein, hemagglutinin, within the plasma membrane are hypothesized to be enriched with cholesterol and sphingolipids. Here, we directly tested this hypothesis by using high-resolution secondary ion mass spectrometry to image the distributions of antibody-labeled hemagglutinin and isotope-labeled cholesterol and sphingolipids in the plasma membranes of fibroblast cells that stably express hemagglutinin. We found that the hemagglutinin clusters were neither enriched with cholesterol nor colocalized with sphingolipid domains. Thus, hemagglutinin clustering and localization in the plasma membrane is not controlled by cohesive interactions between hemagglutinin and liquid-ordered domains enriched with cholesterol and sphingolipids, or from specific binding interactions between hemagglutinin, cholesterol, and/or the majority of sphingolipid species in the plasma membrane.
Topics: 3T3 Cells; Animals; Cell Membrane; Cholesterol; Hemagglutinins; Mice; Sphingolipids
PubMed: 25863057
DOI: 10.1016/j.bpj.2015.02.026 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Mar 2022Influenza B virus is one of the causes for seasonal influenza, which can account for serious illness or even death in some cases. We tested the expression of...
Influenza B virus is one of the causes for seasonal influenza, which can account for serious illness or even death in some cases. We tested the expression of extracellular domain of hemagglutinin (HA-ecto) of influenza B viruses in mammalian cells, and then determined the immunogenicity of HA-ecto in mice. The gene sequence encoding influenza B virus HA-ecto, foldon sequence, and HIS tag was optimized and inserted into pCAGGS vector. The opening reading frame (ORF) of neuraminidase was also cloned into pCAGGS. The pCAGGS-HA-ecto and pCAGGS-NA were co-transfected into 293T cells using linear polyethylenimine. Cell supernatant after transfection was collected after 96 h, and the secreted trimmeric HA-ecto protein was purified by nickel ion affinity chromatography and size exclusion chromatography. Subsequently, the mice were immunized with HA-ecto protein, and the corresponding antibody titers were detected by ELISA and hemagglutination inhibition (HAI) assays. The results showed that soluble trimeric HA-ecto protein could be obtained using mammalian cell expression system. Moreover, trimeric HA-ecto protein, in combination with the adjuvant, induced high levels of ELISA and HAI antibodies against homogenous and heterologous antigens in mice. Thus, the soluble HA-ecto protein expressed in mammalian cells could be used as a recombinant subunit vaccine candidate for influenza B virus.
Topics: Animals; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins; Influenza B virus; Influenza Vaccines; Mammals; Mice; Mice, Inbred BALB C
PubMed: 35355478
DOI: 10.13345/j.cjb.210203