scholarly journals Continuous Reassortment of Clade 2.3.4.4 H5N6 Highly Pathogenetic Avian Influenza Viruses Demonstrating High Risk to Public Health

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 670 ◽  
Author(s):  
Huanan Li ◽  
Qian Li ◽  
Bo Li ◽  
Yang Guo ◽  
Jinchao Xing ◽  
...  
Keyword(s):  
Public Health ◽  
High Risk ◽  
Avian Influenza ◽  
Migratory Birds ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
The World

Since it firstly emerged in China in 2013, clade 2.3.4.4 H5N6 highly pathogenic avian influenza viruses (HPAIVs) has rapidly replaced predominant H5N1 to become the dominant H5 subtype in China, especially in ducks. Not only endemic in China, it also crossed the geographical barrier and emerged in South Korea, Japan, and Europe. Here, we analyzed the genetic properties of the clade 2.3.4.4 H5N6 HPAIVs with full genome sequences available online together with our own isolates. Phylogenetic analysis showed that clade 2.3.4.4 H5N6 HPAIVs continuously reassorted with local H5, H6, and H7N9/H9N2. Species analysis reveals that aquatic poultry and migratory birds became the dominant hosts of H5N6. Adaption to aquatic poultry might help clade 2.3.4.4 H5N6 better adapt to migratory birds, thus enabling it to become endemic in China. Besides, migratory birds might help clade 2.3.4.4 H5N6 transmit all over the world. Clade 2.3.4.4 H5N6 HPAIVs also showed a preference for α2,6-SA receptors when compared to other avian origin influenza viruses. Experiments in vitro and in vivo revealed that clade 2.3.4.4 H5N6 HPAIVs exhibited high replication efficiency in both avian and mammal cells, and it also showed high pathogenicity in both mice and chickens, demonstrating high risk to public health. Considering all the factors together, adaption to aquatic poultry and migratory birds helps clade 2.3.4.4 H5N6 overcome the geographical isolation, and it has potential to be the next influenza pandemic in the world, making it worthy of our attention.

scholarly journals Pathogenesis and Transmission Assessments of Two H7N8 Influenza A Viruses Recently Isolated from Turkey Farms in Indiana Using Mouse and Ferret Models

2016 ◽  
Vol 90 (23) ◽  
pp. 10936-10944 ◽  
Author(s):  
Xiangjie Sun ◽  
Jessica A. Belser ◽  
Joanna A. Pulit-Penaloza ◽  
Hui Zeng ◽  
Amanda Lewis ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Domestic Poultry ◽  
Commercial Turkey

ABSTRACTAvian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional infections of humans in close contact with affected birds. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low-pathogenic avian influenza (LPAI) viruses was confirmed in commercial turkey farms in Indiana. These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, and their virulence in mammalian hosts and the potential risk for human infection are largely unknown. In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicatein vitroin human airway cells andin vivoin mouse and ferret models. Both H7N8 viruses replicated efficientlyin vitroandin vivo, but they exhibited substantial differences in disease severity in mammals. In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact with an inoculated animal, while no transmission of H7N8 HPAI virus was detected. Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health.IMPORTANCEH7 influenza viruses circulate in wild birds in the United States, but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. An H7N8 highly pathogenic avian influenza (HPAI) virus and an H7N8 low-pathogenic avian influenza (LPAI) virus were recently isolated from commercial turkey farms in Indiana. To determine the risk that these influenza viruses pose to humans, we assessed their pathogenesis and transmissionin vitroand in mammalian models. We found that the H7N8 HPAI virus exhibited enhanced virulence, and although transmission was only observed with the H7N8 LPAI virus, the ability of this H7 virus to transmit in a mammalian host and quickly evolve to a more virulent strain is cause for concern. Our findings offer important insight into the potential for emerging H7 avian influenza viruses to acquire the ability to cause disease and transmit among mammals.

scholarly journals In Vitro Profiling of Laninamivir-Resistant Substitutions in N3 to N9 Avian Influenza Virus Neuraminidase Subtypes and Their Association with In Vivo Susceptibility

2020 ◽  
Vol 95 (1) ◽  
Author(s):  
Ju Hwan Jeong ◽  
Won-Suk Choi ◽  
Khristine Joy C. Antigua ◽  
Young Ki Choi ◽  
Elena A. Govorkova ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Resistance Mechanisms ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Enzyme Active Site ◽  
Chemical Structures ◽  
Resistance Markers ◽  
Long Acting

ABSTRACT Laninamivir (LAN) is a long-acting neuraminidase (NA) inhibitor (NAI) with a similar binding profile in the influenza NA enzyme active site as those of other NAIs, oseltamivir (OS), zanamivir (ZAN), and peramivir, and may share common resistance markers with these NAIs. We screened viruses with NA substitutions previously found during OS and ZAN selection in avian influenza viruses (AIVs) of the N3 to N9 subtypes for LAN susceptibility. Of the 72 NA substitutions, 19 conferred resistance to LAN, which ranged from 11.2- to 549.8-fold-decreased inhibitory activity over that of their parental viruses. Ten NA substitutions reduced the susceptibility to all four NAIs, whereas the remaining 26 substitutions yielded susceptibility to one or more NAIs. To determine whether the in vitro susceptibility of multi-NAI-resistant AIVs is associated with in vivo susceptibility, we infected BALB/c mice with recombinant AIVs with R292K (ma81K-N3R292K) or Q136K (ma81K-N8Q136K) NA substitutions, which impart in vitro susceptibility only to LAN or OS, respectively. Both ma81K-N3R292K and ma81K-N8Q136K virus-infected mice exhibited reduced weight loss, mortality, and lung viral titers when treated with their susceptible NAIs, confirming the in vitro susceptibility of these substitutions. Together, LAN resistance profiling of AIVs of a range of NA subtypes improves the understanding of NAI resistance mechanisms. Furthermore, the association of in vitro and in vivo NAI susceptibility indicates that our models are useful tools for monitoring NAI susceptibility of AIVs. IMPORTANCE The chemical structures of neuraminidase inhibitors (NAIs) possess similarities, but slight differences can result in variable susceptibility of avian influenza viruses (AIVs) carrying resistance-associated NA substitutions. Therefore, comprehensive susceptibility profiling of these substitutions in AIVs is critical for understanding the mechanism of antiviral resistance. In this study, we profiled resistance to the anti-influenza drug laninamivir in AIVs with substitutions known to impart resistance to other NAIs. We found 10 substitutions that conferred resistance to all four NAIs tested. On the other hand, we found that the remaining 26 NA substitutions were susceptible to at least one or more NAIs and showed for a small selection that in vitro data predicted in vivo behavior. Therefore, our findings highlight the usefulness of screening resistance markers in NA enzyme inhibition assays and animal models of AIV infections.

scholarly journals PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range

2020 ◽  
Vol 95 (1) ◽  
Author(s):  
Yasuha Arai ◽  
Norihito Kawashita ◽  
Emad Mohamed Elgendy ◽  
Madiha Salah Ibrahim ◽  
Tomo Daidoji ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Host Range ◽  
Human Cells ◽  
Influenza Viruses ◽  
Human Adaptation ◽  
Avian Influenza Viruses ◽  
H5n1 Influenza

ABSTRACT Adaptive mutations and/or reassortments in avian influenza virus polymerase subunits PA, PB1, and PB2 are one of the major factors enabling the virus to overcome the species barrier to infect humans. The majority of human adaptation polymerase mutations have been identified in PB2; fewer adaptation mutations have been characterized in PA and PB1. Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and generally carry the human adaptation PB2-E627K substitution during their dissemination in nature. In this study, we identified other human adaptation polymerase mutations by analyzing phylogeny-associated PA mutations that H5N1 clade 2.2.1 viruses have accumulated during their evolution in the field. This analysis identified several PA mutations that produced increased replication by contemporary clade 2.2.1.2 viruses in vitro in human cells and in vivo in mice compared to ancestral clade 2.2.1 viruses. The PA mutations acted cooperatively to increase viral polymerase activity and replication in both avian and human cells, with the effect being more prominent in human cells at 33°C than at 37°C. These results indicated that PA mutations have a role in establishing contemporary clade 2.2.1.2 virus infections in poultry and in adaptation to infect mammals. Our study provided data on the mechanism for PA mutations to accumulate during avian influenza virus evolution and extend the viral host range. IMPORTANCE Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and have caused the highest number of human H5N1 influenza cases worldwide, presenting a serious global public health threat. These viruses may have the greatest evolutionary potential for adaptation from avian hosts to human hosts. Using a comprehensive phylogenetic approach, we identified several novel clade 2.2.1 virus polymerase mutations that increased viral replication in vitro in human cells and in vivo in mice. These mutations were in the polymerase PA subunit and acted cooperatively with the E627K mutation in the PB2 polymerase subunit to provide higher replication in contemporary clade 2.2.1.2 viruses than in ancestral clade 2.2.1 viruses. These data indicated that ongoing clade 2.2.1 dissemination in the field has driven PA mutations to modify viral replication to enable host range expansion, with a higher public health risk for humans.

scholarly journals Avian Influenza & Human Health

2014 ◽  
Vol 5 (1) ◽  
pp. 35-38
Author(s):  
Prosun Roy ◽  
SM Rashed-ul Islam ◽  
Farhana Rahman ◽  
Md Mahmudur Rahman Siddiqui
Keyword(s):  
Avian Influenza ◽  
Human Health ◽  
Viral Infections ◽  
Influenza Pandemic ◽  
Animal Health ◽  
Genetic Mutation ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
The World

The world is now under human pandemic threat by avian influenza viruses. As the human, animal and the environment interact closely from the dawn of the civilization, human health is tremendously influenced by animal health and their health issues. In last few centuries the world has suffered a number of influenza pandemics killing millions of people such as Spanish Flu (1918), Asiatic or Russian Flu (1889-1890), Asian Flu (1957-1958) etc. The exceptional capability of genetic mutation of the influenza viruses offered threats to the whole world time to time. Like all other countries Bangladesh also not away from the heat of the situation. Human cases of avian influenza subtype H1N1, H3, H5N1, and H9N2 have already been reported from Bangladesh. This article reviews the information available on pandemic potential of avian influenza viruses. The article also sheds light on different avian influenza viruses along with some emphasis on clinical and preventive aspects of the avian influenza viral infections, and on avian influenza pandemic preparedness of Bangladesh. DOI: http://dx.doi.org/10.3329/akmmcj.v5i1.18839 Anwer Khan Modern Medical College Journal Vol. 5, No. 1: January 2014, Pages 35-38

scholarly journals Pathogenic Assessment of Avian Influenza Viruses in Migratory Birds

2021 ◽  
pp. 1-40
Author(s):  
Eun-Ha Kim ◽  
Young-ll Kim ◽  
Se Mi Kim ◽  
Kwang-Min Yu ◽  
Mark Anthony B. Casel ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Migratory Birds ◽  
Influenza Viruses ◽  
Avian Influenza Viruses

scholarly journals Ecology of H3 avian influenza viruses in Korea and assessment of their pathogenic potentials

2008 ◽  
Vol 89 (4) ◽  
pp. 949-957 ◽  
Author(s):  
Min-Suk Song ◽  
Taek-Kyu Oh ◽  
Ho Jin Moon ◽  
Dai-Woon Yoo ◽  
Eun Ho Lee ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Wild Bird ◽  
Migratory Birds ◽  
Influenza Viruses ◽  
Interspecies Transmission ◽  
Avian Influenza Viruses ◽  
Backyard Poultry ◽  
Live Poultry ◽  
Live Poultry Markets

To determine the genetic origins of novel H3 avian influenza viruses of chickens and ducks in Korea, genetic characterization of H3 avian influenza viruses isolated from live poultry markets and migratory aquatic birds in South Korea during 2004–2006 was conducted. Phylogenetic analysis revealed that at least four novel genotypes of H3N2 and two genotypes of H3N6 avian influenza viruses were co-circulating in backyard poultry of Korea. The viruses were reassortants between H9N2 viruses of Korean chickens and unknown influenza viruses of migratory birds. Genetic comparison of H3 viruses from live bird markets with those from wild bird isolates revealed that certain gene segments of wild bird isolates are related closely to those of Korean group H9N2 viruses isolated from live poultry markets in 2003. Furthermore, animal-challenge studies demonstrated that the pathogenicity of certain avian H3 influenza viruses was altered due to reassortment, leading to H3 avian influenza viruses in Korea that can potentially expand their host range to include mammals. These studies emphasize the continuing need to monitor backyard poultry at live poultry markets to better understand interspecies transmission and the emergence of novel influenza viruses that have the potential to infect humans.

scholarly journals Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 143
Author(s):  
Gendeal M. Fadlallah ◽  
Fuying Ma ◽  
Zherui Zhang ◽  
Mengchan Hao ◽  
Juefu Hu ◽  
...  
Keyword(s):  
Avian Influenza ◽  
North American ◽  
Human Infection ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Lethal Challenge ◽  
Protective Antibodies ◽  
H7 Subtype ◽  
H7n3 Virus

H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses require the development of cross-protective vaccine candidates. In this study, a methodology called computationally optimized broadly reactive antigen (COBRA) was used to develop four consensus H7 antigens (CH7-22, CH7-24, CH7-26, and CH7-28). In vitro experiments confirmed the binding of monoclonal antibodies to the head and stem domains of cell surface-expressed consensus HAs, indicating display of their antigenicity. Immunization with DNA vaccines encoding the four antigens was evaluated in a mouse model. Broadly reactive antibodies against H7 viruses from Eurasian and North American lineages were elicited and detected by binding, inhibition, and neutralizing analyses. Further infection with Eurasian H7N9 and North American H7N3 virus strains confirmed that CH7-22 and CH7-24 conferred the most effective protection against hetero-lethal challenge. Our data showed that the consensus H7 vaccines elicit a broadly reactive, protective response against Eurasian and North American lineage H7 viruses, which are suitable for development against other zoonotic influenza viruses.

scholarly journals Lessons From Influenza Pandemics of the Last 100 Years

2019 ◽  
Author(s):  
Arnold S Monto ◽  
Keiji Fukuda
Keyword(s):  
Avian Influenza ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
Risk Groups ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
Fundamental Difficulty ◽  
1918 Influenza ◽  
The Impact

Abstract Seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. Recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. Review of features of the 1918 influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. Key among such issues are likely risk groups and which interventions to employ. Past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. While a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. Improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza.

scholarly journals H5N1 infections in cats – public health implications

2006 ◽  
Vol 11 (15) ◽  
Author(s):  
Collective Influenza team (ECDC)
Keyword(s):  
Public Health ◽  
Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Animal Group ◽  
Health Implications ◽  
Natural Reservoir ◽  
Pathogenic Avian Influenza ◽  
Low Pathogenic Avian Influenza

The natural reservoir of influenza viruses is generally considered to be wild waterbirds. In this animal group, many species of influenza viruses circulate without seeming to cause much disease, and are therefore known as ‘low pathogenic’ avian influenza viruses

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