The T160A hemagglutinin substitution affects not only receptor binding property but also transmissibility of H5N1 clade 2.3.4 avian influenza virus in guinea pigs

AbstractWe generated and characterized site-directed HA mutants on the genetic backbone of H5N1 clade 2.3.4 virus preferentially binding to α-2,3 receptors in order to identify the key determinants in hemagglutinin rendering the dual affinity to both α-2,3 (avian-type) and α-2,6 (human-type) linked sialic acid receptors of the current clade 2.3.4.4 H5NX subtype avian influenza reassortants. The results show that the T160A substitutio n resulted in the loss of a glycosylation site at 158N and led not only to enhanced binding specificity for human-type receptors but also transmissibility among guinea pigs, which could be considered as an important molecular marker for assessing pandemic potential of H5 subtype avian influenza isol ates.
Source: Veterinary Research - Category: Veterinary Research Source Type: research

Related Links:

Contributors : Ariel Rodriguez-Frandsen ; Laura Martin-Sancho ; Anshu P Gounder ; Sumit K ChandaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensInfluenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, and sporadic pandemics due to human adaptation of pathogenic strains. Efficient replication of IAV in different species is, in part, dictated by its ability to exploit the genetic environment of the host cell. To investigate IAV tropism in human cells, we evaluated the replication of IAV strains in a diverse subset of epithelial cell lines. HeLa cells ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Abstract BACKGROUND: The emergence and spread of highly pathogenic avian influenza (H5N1) viruses have raised global concerns of a possible human pandemic, spurring efforts towards H5N1 influenza vaccine development and improvements in vaccine administration methods. We previously showed that a prime-boost vaccination strategy induces robust and broadly cross-reactive antibody responses against the hemagglutinin globular head domain. Here, we specifically measure antibodies against the conserved hemagglutinin stem region in serum samples obtained from the prior study to determine whether stalk-reactive antibodies ...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
yn Kobasa Influenza A viruses (IAVs) are important animal and human emerging and re-emerging pathogens that are responsible for yearly seasonal epidemics and sporadic pandemics. IAVs cause a wide range of clinical illnesses, from relatively mild infections by seasonal strains, to acute respiratory distress during infections with highly pathogenic avian IAVs (HPAI). For this study, we infected A549 human lung cells with lab prototype A/PR/8/34 (H1N1) (PR8), a seasonal H1N1 (RV733), the 2009 pandemic H1N1 (pdm09), or with two avian strains, an H5N1 HPAI strain or an H7N9 strain that has low pathogenicity in birds but hig...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
In this study, we identified four amantadine-resistant M2 mutants among avian and human influenza A H5N1 strains circulating between 2002 to 2019: the single S31N and V27A mutants, and the S31N/L26I and S31N/V27A double mutants. Herein, utilizing two-electrode voltage clamp (TEVC) assays, we screened a panel of structurally diverse M2 inhibitors against these single and double mutant channels. Three compounds 6, 7, and 15 were found to significantly block all three M2 mutants: M2-S31N, M2-S31N/L26I, and M2-S31N/V27A. Using recombinant viruses generated from reverse genetics, we further showed that these compounds also inhi...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research
In this study, we investigated the delivery of insect cell culture-derived recombinant hemagglutinin protein (HA) of A/H5N1/Vietnam/1203/2004 virus using CaPNP. We evaluated the vaccine immunogenicity in mice following two intramuscular doses of 3 μg antigen combined with escalating doses of CaPNP. Our data showed CaPNP-adjuvanted HA(H5N1) vaccines eliciting significantly higher IgG, hemagglutination inhibition, and virus neutralization titers compared to non-adjuvanted vaccine. Among the four adjuvant doses that were tested, CaPNP at 0.24% final concentration elicited the highest IgG and neutralizing antibody tite...
Source: AAPS PharmSciTech - Category: Drugs & Pharmacology Authors: Tags: AAPS PharmSciTech Source Type: research
The highly pathogenic (HP) avian influenza virus (AIV), H5N1 and reassortant H5-subtype HPAIVs, H5N2, H5N6, and H5N8, cause high mortality in domestic birds, resulting in economic losses in the poultry industry. H5N1 and H5N6 also pose significant public health risks and H5N1 viruses are a permanent pandemic threat. To control HPAIVs, eukaryotic expression systems have traditionally been exploited to produce vaccines based on hemagglutinin (HA), a protective viral antigen. In contrast, we used a bacterial expression system to produce vaccine targeting the HA protein. A fragment of the HA ectodomain from H5N1, with a multib...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractAvian influenza viruses (AIVs) circulate globally, spilling over into domestic poultry and causing zoonotic infections in humans. Fortunately, AIVs are not yet capable of causing sustained human-to-human infection; however, AIVs are still a high risk as future pandemic strains, especially if they acquire further mutations that facilitate human infection and/or increase pathogenesis. Molecular characterization of sequencing data for known genetic markers associated with AIV adaptation, transmission, and antiviral resistance allows for fast, efficient assessment of AIV risk. Here we summarize and update the current k...
Source: Virus Genes - Category: Genetics & Stem Cells Source Type: research
AbstractThe interferon-induced transmembrane protein 3 (IFITM3) gene is classified as a small interferon-stimulated gene and is associated with a broad spectrum of antiviral functions against several fatal enveloped viruses, including influenza A viruses (IAVs). The rs12252 single nucleotide polymorphism (SNP) of theIFITM3 gene in humans was associated with susceptibility to H1N1 influenza in a 2009 pandemic. In addition, overexpression of the IFITM3 protein potently inhibits the highly pathogenic avian influenza H5N1 virus in ducks and chickens. Although chickens are a major host of influenza viruses and theIFITM3 gene pa...
Source: Veterinary Research Communications - Category: Veterinary Research Source Type: research
The highly pathogenic H5N1 avian influenza virus (HPAIV) was first identified in China in 1996 [A/goose/Guangdong/1/1996 (Gs/GD)] and infected the human population in Hong Kong in 1997, with 18 recorded cases resulting in six deaths.[1,2]1,2 Since 2003, Gs/GD lineage H5N1 HPAIV infection in humans has been reported in 16 countries, with 860 laboratory-confirmed cases and 454 deaths as of 2018.3 Although human-to-human transmission has not been documented, H5N1 HPAIV has the potential to cause an influenza pandemic.
Source: Journal of Infection - Category: Infectious Diseases Authors: Source Type: research
The highly pathogenic H5N1 avian influenza virus (HPAIV) was first identified in China in 1996 [A/goose/Guangdong/1/1996 (Gs/GD)] and infected the human population in Hong Kong in 1997, with 18 recorded cases resulting in six deaths.1, 2 Since 2003, Gs/GD lineage H5N1 HPAIV infection in humans has been reported in 16 countries, with 860 laboratory-confirmed cases and 454 deaths as of 2018.3 Although human-to-human transmission has not been documented, H5N1 HPAIV has the potential to cause an influenza pandemic.
Source: Journal of Infection - Category: Infectious Diseases Authors: Source Type: research
More News: Bird Flu | Flu Pandemic | Genetics | H5N1 | Influenza | Pandemics | Veterinary Research