scholarly journals Site-Specific Glycan-Masking/Unmasking Hemagglutinin Antigen Design to Elicit Broadly Neutralizing and Stem-Binding Antibodies Against Highly Pathogenic Avian Influenza H5N1 Virus Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Hsuan Chen ◽  
Ya-Lin Yang ◽  
Jia-Tsrong Jan ◽  
Chung-Chu Chen ◽  
Suh-Chin Wu
Keyword(s):  
Avian Influenza ◽  
Neutralizing Antibodies ◽  
Reverse Genetics ◽  
Highly Pathogenic Avian Influenza ◽  
Mdck Cells ◽  
Highly Pathogenic ◽  
Site Specific ◽  
Booster Immunization ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1

The highly pathogenic avian influenza (HPAI) H5N1 viruses with the capability of transmission from birds to humans have a serious impact on public health. To date, HPAI H5N1 viruses have evolved into ten antigenically distinct clades that could cause a mismatch of vaccine strains and reduce vaccine efficacy. In this study, the glycan masking and unmasking strategies on hemagglutinin antigen were used for designing two antigens: H5-dm/st2 and H5-tm/st2, and investigated for their elicited immunity using two-dose recombinant H5 (rH5) immunization and a first-dose adenovirus vector prime, followed by a second-dose rH5 protein booster immunization. The H5-dm/st2 antigen was found to elicit broadly neutralizing antibodies against different H5N1 clade/subclade viruses, as well as more stem-binding antibodies to inhibit HA-facilitated membrane fusion activity. Mice immunized with the H5-dm/st2 antigen had a higher survival rate when challenged with homologous and heterologous clades of H5N1 viruses. Mutant influenza virus replaced with the H5-dm/st2 gene generated by reverse genetics (RG) technology amplified well in MDCK cells and embryonated chicken eggs. Again, the inactivated H5N1-dm/st2 RG virus elicited more potent cross-clade neutralizing and anti-fusion antibodies in sera. Therefore, the H5N1-dm/st2 RG virus with the site-specific glycan-masking on the globular head and the glycan-unmasking on the stem region of H5 antigen can be used for further development of cross-protective H5N1 vaccines.

scholarly journals Substitution of I222L-E119V in neuraminidase from highly pathogenic avian influenza H7N9 virus exhibited synergistic resistance effect to oseltamivir in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Tang ◽  
Rongbao Gao ◽  
Liqi Liu ◽  
Shuxia Zhang ◽  
Jia Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Avian Influenza ◽  
Reverse Genetics ◽  
Highly Pathogenic Avian Influenza ◽  
Mdck Cells ◽  
Replication Capacity ◽  
H7n9 Virus ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza

AbstractThat the high frequency and good replication capacity of strains with reduced susceptibility to neuraminidase inhibitors (NAIs) in highly pathogenic avian influenza H7N9 (HPAI H7N9) virus made it a significance to further study its drug resistance. HPAI H7N9 viruses bearing NA I222L or E119V substitution and two mutations of I222L-E119V as well as their NAIs-sensitive counterpart were generated by reverse genetics for NA inhibition test and replication capability evaluation in vitro. The attenuated H7N9/PR8 recombinant viruses were developed to study the pathogenicity and drug resistance brought by the above substitutions to mice. The IC50 fold change of oseltamivir to HPAI H7N9 with NA222L-119V is 306.34 times than that of its susceptible strain, and 3.5 times than the E119V mutant virus. HPAI H7N9 bearing NA222L-119V had good replication ability with peak value of more than 6log10 TCID50/ml in MDCK cells. H7N9/PR8 virus bearing NA222L-119V substitutions leaded to diffuse pneumonia, significant weight loss and fatality in mice. NA E119V made H7N9/PR8 virus resistant to oseltamivir, and I222L-E119V had synergistic resistance to oseltamivir in mice. Due to the good fitness of drug resistant strains of HPAI H7N9 virus, it is necessary to strengthen drug resistance surveillance and new drug research.

scholarly journals Highly Pathogenic Avian Influenza Viruses at the Wild–Domestic Bird Interface in Europe: Future Directions for Research and Surveillance

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 212
Author(s):  
Josanne H. Verhagen ◽  
Ron A. M. Fouchier ◽  
Nicola Lewis
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Wild Birds ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Future Directions ◽  
Pathogenic Avian Influenza ◽  
Domestic Bird ◽  
Hpai H5n1 ◽  
Host Identification

Highly pathogenic avian influenza (HPAI) outbreaks in wild birds and poultry are no longer a rare phenomenon in Europe. In the past 15 years, HPAI outbreaks—in particular those caused by H5 viruses derived from the A/Goose/Guangdong/1/1996 lineage that emerged in southeast Asia in 1996—have been occuring with increasing frequency in Europe. Between 2005 and 2020, at least ten HPAI H5 incursions were identified in Europe resulting in mass mortalities among poultry and wild birds. Until 2009, the HPAI H5 virus outbreaks in Europe were caused by HPAI H5N1 clade 2.2 viruses, while from 2014 onwards HPAI H5 clade 2.3.4.4 viruses dominated outbreaks, with abundant genetic reassortments yielding subtypes H5N1, H5N2, H5N3, H5N4, H5N5, H5N6 and H5N8. The majority of HPAI H5 virus detections in wild and domestic birds within Europe coincide with southwest/westward fall migration and large local waterbird aggregations during wintering. In this review we provide an overview of HPAI H5 virus epidemiology, ecology and evolution at the interface between poultry and wild birds based on 15 years of avian influenza virus surveillance in Europe, and assess future directions for HPAI virus research and surveillance, including the integration of whole genome sequencing, host identification and avian ecology into risk-based surveillance and analyses.

Opposite outcomes of the within-host competition between highly and low pathogenic H5N8 avian influenza viruses in chickens compared to ducks

2021 ◽  
Author(s):  
Pierre Bessière ◽  
Thomas Figueroa ◽  
Amelia Coggon ◽  
Charlotte Foret-Lucas ◽  
Alexandre Houffschmitt ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Reverse Genetics ◽  
Highly Pathogenic Avian Influenza ◽  
Viral Evolution ◽  
Influenza Viruses ◽  
Poultry Production ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Low Pathogenic Avian Influenza

Highly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8 LP increased H5N8 HP replication and pathogenesis. By contrast, the H5N8 LP antagonized H5N8 HP replication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8 LP , which correlated with H5N8 HP inhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variants interactions in viral evolution. IMPORTANCE Highly pathogenic avian influenza viruses represent a threat to poultry production systems and to human health because of their impact on food security and because of their zoonotic potential. It is therefore crucial to better understand how these viruses emerge. Using a within-host competition model between highly and low pathogenic avian influenza viruses, we provide evidence that highly pathogenic avian influenza viruses could be more likely to emerge in chickens than in ducks. These results have important implications for highly pathogenic avian influenza virus emergence prevention and they underscore the importance of within-host viral variants interactions in virus evolution.

scholarly journals Proteomics Analysis of Differential Expression of Lung Proteins In Response To Highly Pathogenic Avian Influenza Virus Infection In Chicken

2021 ◽  
Author(s):  
Periyasamy Vijayakumar ◽  
Ashwin Ashok Raut ◽  
Santhalembi Chingtham ◽  
Harshad V Murugkar ◽  
Diwakar D. Kulkarni ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
H5n1 Virus ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Virus Infection ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Host Interaction ◽  
Hpai H5n1

Abstract Elucidation of molecular pathogenesis underlying virus-host interaction is important for the development of new diagnostic and therapeutic strategies against highly pathogenic avian influenza (HPAI) infection in chicken. However, chicken HPAI viral pathogenesis is not completely understood. To elucidate the intracellular signaling pathways and critical host proteins associated with influenza pathogenesis, we characterized the lung proteome of chicken infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala). The chicken mass spectra data sets comprised1, 47, 451 MS scans and 19, 917 MS/MS scans. At local FDR 5% level, we identified total 3313 chicken proteins with presence of at least one unique peptide. At 12 hrs, 247 proteins are downregulated while 1754 proteins are downregulated at 48 hrs indicating that the host has succumbed to infection. There is expression of proteins of the predominant signaling pathways, such as TLR, RLR, NLR and JAK-STAT signaling. Activation of these pathways is associated with cytokine storm effect and thus may be the cause of severity of HPAI H5N1 infection in chicken. Further we identified proteins like MyD88, IKBKB, IRAK4, RELA, and MAVS involved in the critical signaling pathways and some other novel proteins (HNF4A, ELAVL1, FN1, COPS5, CUL1, BRCA1 and FYN) as main hub proteins that might play important roles in influenza pathogenesis in chicken. Taken together, we characterized the signaling pathways and the proteomic determinants responsible for disease pathogenesis in chicken infected with HPAI H5N1 virus.

scholarly journals The Pattern of Highly Pathogenic Avian Influenza H5N1 Outbreaks in South Asia

2019 ◽  
Vol 4 (4) ◽  
pp. 138 ◽  
Author(s):  
Chowdhury ◽  
Hossain ◽  
Ghosh ◽  
Ghosh ◽  
Hossain ◽  
...  
Keyword(s):  
Avian Influenza ◽  
South Asia ◽  
Highly Pathogenic Avian Influenza ◽  
Winter Season ◽  
Temporal Distribution ◽  
Influenza Viruses ◽  
World Health ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1

Highly pathogenic avian influenza (HPAI) H5N1 has caused severe illnesses in poultry and in humans. More than 15,000 outbreaks in domestic birds from 2005 to 2018 and 861 human cases from 2003 to 2019 were reported across the world to OIE (Office International des Epizooties) and WHO (World Health Organization), respectively. We reviewed and summarized the spatial and temporal distribution of HPAI outbreaks in South Asia. During January 2006 to June 2019, a total of 1063 H5N1 outbreaks in birds and 12 human cases for H5N1 infection were reported to OIE and WHO, respectively. H5N1 outbreaks were detected more in the winter season than the summer season (RR 5.11, 95% CI: 4.28–6.1). Commercial poultry were three times more likely to be infected with H5N1 than backyard poultry (RR 3.47, 95% CI: 2.99–4.01). The highest number of H5N1 outbreaks was reported in 2008, and the smallest numbers were reported in 2014 and 2015. Multiple subtypes of avian influenza viruses and multiple clades of H5N1 virus were detected. Early detection and reporting of HPAI viruses are needed to control and eliminate HPAI in South Asia.

scholarly journals Highly Pathogenic Avian Influenza (H5N1) Landscape Suitability Varies by Wetland Habitats and the Degree of Interface between Wild Waterfowl and Poultry in India

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1290
Author(s):  
Michael G. Walsh ◽  
Siobhan M. Mor ◽  
Shah Hossain
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Animal Health ◽  
Local Scale ◽  
Highly Pathogenic ◽  
Wetland Habitat ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1 ◽  
Landscape Suitability ◽  
Wild Waterfowl

Highly pathogenic avian influenza (HPAI) virus, subtype H5N1, constitutes one of the world’s most important health and economic concerns given the catastrophic impact of epizootics on the poultry industry, the high mortality attending spillover in humans, and its potential as a source subtype for a future pandemic. Nevertheless, we still lack an adequate understanding of HPAI H5N1 epidemiology and infection ecology. The nature of the wild waterfowl–poultry interface, and the sharing of diverse wetland habitat among these birds, currently underscore important knowledge gaps. India has emerged as a global hotspot for HPAI H5N1, while also providing critical wintering habitat for many species of migratory waterfowl and year-round habitat for several resident waterfowl species. The current study sought to examine the extent to which the wild waterfowl–poultry interface, varied wetland habitat, and climate influence HPAI H5N1 epizootics in poultry in India. Using World Organisation for Animal Health reported outbreaks, this study showed that the wild waterfowl–poultry interface and lacustrine, riparian, and coastal marsh wetland systems were strongly associated with landscape suitability, and these relationships varied by scale. Although increasing poultry density was associated with increasing risk, this was only the case in the absence of wild waterfowl habitat, and only at a local scale. In landscapes increasingly shared between wild waterfowl and poultry, suitability was greater among lower density poultry, again at a local scale only. These findings provide further insight into the occurrence of HPAI H5N1 in India and suggest important landscape targets for blocking the waterfowl–poultry interface to interrupt virus transmission and prevent future outbreaks.

scholarly journals Mortality and Pathology Associated with Highly Pathogenic Avian Influenza H5N1 Outbreaks in Commercial Poultry Production Systems in Nigeria

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Olatunde Babatunde Akanbi ◽  
Victor Olusegun Taiwo
Keyword(s):  
Avian Influenza ◽  
Production Systems ◽  
Highly Pathogenic Avian Influenza ◽  
Poultry Production ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1 ◽  
Commercial Poultry ◽  
The One ◽  
Influenza H5n1

Commercial layer-type, pullet, cockerel, and broiler chicken flocks infected with highly pathogenic avian influenza (HPAI) H5N1 in Nigeria between 2006 and 2008 were investigated for morbidity, mortality, and pathology. Of the one hundred and fifty-three (153) farms confirmed with HPAI infection, one hundred and twenty-seven (127) were layer-type farms, nine (9) were pullet and broiler farms each, and eight (8) were cockerel rearing farms. This study revealed the morbidity and mortality of a total of 939,620 commercial layer chickens, 16,421 pullets, 3,109 cockerels, and 6,433 broilers. Mortality rates were 11.11% in commercial layers, 26.84% in pullets, 45.51% in cockerels, and 73.92% in broilers in a total of eighteen (18) states and the Federal Capital Territory, Abuja. A total of 316 carcasses were examined of which 248 were commercial layer, 25 were pullet, 14 were cockerel, and 29 were broiler. Main clinical and pathologic findings were observed in the nervous, circulatory, respiratory, integumentary, musculoskeletal, hemopoietic, gastrointestinal, and reproductive systems and, occasionally, lesions were generally nonspecific and multisystemic. Lesions occurred more frequently, severely, and in most of the carcasses examined, irrespective of chicken type.

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