scholarly journals Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses

2011 ◽  
Vol 8 (1) ◽  
Author(s):  
Kyoko Shinya ◽  
Tadashi Okamura ◽  
Setsuko Sueta ◽  
Noriyuki Kasai ◽  
Motoko Tanaka ◽  
...  
Keyword(s):  
Influenza Viruses ◽  
Toll Like Receptor ◽  
Highly Pathogenic ◽  
Lethal Infection

scholarly journals Characterization of Four Novel H5N6 Avian Influenza Viruses with the Internal Genes from H5N1 and H9N2 Viruses and Experimental Challenge of Chickens Vaccinated with Current Commercially Available H5 Vaccines

2020 ◽  
Author(s):  
Peng Chen ◽  
Pengwei Zhao ◽  
Jun Chu ◽  
Junda Zhu ◽  
Qiuchen Li ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Lethal Infection ◽  
Internal Gene ◽  
Reassortant Viruses ◽  
Virus Strains ◽  
Experimental Challenge

Since 2014, highly pathogenic avian influenza H5N6 viruses have been responsible for outbreaks in poultry. In this study, four H5N6 virus strains were isolated from fecal samples of sick white ducks and dead chickens in Shandong in 2019. These H5N6 viruses were triple-reassortant viruses that have not been previously characterized. Their HA genes were derived from the H5 viruses and were closely related to the vaccine strain Re-11. Their NA genes all fell into the N6-like lineage and the internal gene were derived from H5N1 and H9N2 viruses. They all showed high pathogenicity in mice and caused lethal infection with high rates of transmission in chickens. Moreover, the SPF chickens inoculated with the current used vaccine in China were completely protected from these four H5N6 viruses. Our study indicated the necessity of continued surveillance for H5 IAV and the importance of timely update of vaccine strains in poultry industry.

scholarly journals Morpholino oligomers targeting the PB1 and NP genes enhance the survival of mice infected with highly pathogenic influenza A H7N7 virus

2008 ◽  
Vol 89 (4) ◽  
pp. 939-948 ◽  
Author(s):  
Gülsah Gabriel ◽  
Alexandra Nordmann ◽  
David A. Stein ◽  
Patrick L. Iversen ◽  
Hans-Dieter Klenk
Keyword(s):  
Influenza A ◽  
Therapeutic Strategy ◽  
Mdck Cells ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Acid Analogue ◽  
Lethal Infection ◽  
Translation Start ◽  
Phosphorodiamidate Morpholino Oligomers ◽  
Reduce Gene Expression

Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded nucleic acid-analogue antisense agents that enter cells readily and can reduce gene expression by steric blocking of complementary RNA (cRNA) sequences. Here, we tested a panel of PPMO designed to target conserved sequences in the RNA genome segments encoding polymerase subunits of a highly pathogenic mouse-adapted influenza A virus (SC35M; H7N7). Three PPMO, targeting the translation start site region of PB1 or NP mRNA or the 3′-terminal region of NP viral RNA (vRNA), potently inhibited virus replication in MDCK cells. Primer extension assays showed that treatment with any of the effective PPMO led to markedly reduced levels of mRNA, cRNA and vRNA. Initially, the potential toxicity of a range of intranasally administered PPMO doses was evaluated, by measuring their effect on body weight of uninfected mice. Subsequently, a non-toxic dosing regimen was used to investigate the effect of various PPMO on SC35M infection in a mouse model. Mice administered intranasal treatment of PPMO targeting the PB1-AUG region or NP vRNA, at 3 μg per dose, given once 3 h before and once 2 days after intranasal infection with 10×LD50 of SC35M, showed a 2 log10 reduction of viral titre in the lungs and 50 % survival for the 16 day duration of the experiment, whereas the NP-AUG-targeted PPMO treatment resulted in 30 % survival of an otherwise lethal infection. These data suggest that PPMO provide a useful reagent to investigate influenza virus molecular biology and may constitute a therapeutic strategy against highly pathogenic influenza viruses.

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.

scholarly journals Antibodies to Highly Pathogenic A/H5Nx (Clade 2.3.4.4) Influenza Viruses in the Sera of Vietnamese Residents

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 394
Author(s):  
Tatyana Ilyicheva ◽  
Vasily Marchenko ◽  
Olga Pyankova ◽  
Anastasia Moiseeva ◽  
Tran Thi Nhai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Wide Spectrum ◽  
Influenza Viruses ◽  
Serum Samples ◽  
Socialist Republic ◽  
Highly Pathogenic ◽  
Virus Variant ◽  
Human Sera ◽  
Hemagglutinin Inhibition

To cause a pandemic, an influenza virus has to overcome two main barriers. First, the virus has to be antigenically new to humans. Second, the virus has to be directly transmitted from humans to humans. Thus, if the avian influenza virus is able to pass the second barrier, it could cause a pandemic, since there is no immunity to avian influenza in the human population. To determine whether the adaptation process is ongoing, analyses of human sera could be conducted in populations inhabiting regions where pandemic virus variant emergence is highly possible. This study aimed to analyze the sera of Vietnamese residents using hemagglutinin inhibition reaction (HI) and microneutralization (MN) with A/H5Nx (clade 2.3.4.4) influenza viruses isolated in Vietnam and the Russian Federation in 2017–2018. In this study, we used sera from 295 residents of the Socialist Republic of Vietnam collected from three groups: 52 samples were collected from households in Nam Dinh province, where poultry deaths have been reported (2017); 96 (2017) and 147 (2018) samples were collected from patients with somatic but not infectious diseases in Hanoi. In all, 65 serum samples were positive for HI, at least to one H5 virus used in the study. In MN, 47 serum samples neutralizing one or two viruses at dilutions of 1/40 or higher were identified. We postulate that the rapidly evolving A/H5Nx (clade 2.3.4.4) influenza virus is possibly gradually adapting to the human host, insofar as healthy individuals have antibodies to a wide spectrum of variants of that subtype.

scholarly journals H5N2 Avian Influenza Outbreak in Texas in 2004: the First Highly Pathogenic Strain in the United States in 20 Years?

2005 ◽  
Vol 79 (17) ◽  
pp. 11412-11421 ◽  
Author(s):  
Chang-Won Lee ◽  
David E. Swayne ◽  
Jose A. Linares ◽  
Dennis A. Senne ◽  
David L. Suarez
Keyword(s):  
United States ◽  
Amino Acid ◽  
Avian Influenza ◽  
Cleavage Site ◽  
Basic Amino Acid ◽  
The United States ◽  
Influenza Viruses ◽  
Single Point Mutation ◽  
Highly Pathogenic

ABSTRACT In early 2004, an H5N2 avian influenza virus (AIV) that met the molecular criteria for classification as a highly pathogenic AIV was isolated from chickens in the state of Texas in the United States. However, clinical manifestations in the affected flock were consistent with avian influenza caused by a low-pathogenicity AIV and the representative virus (A/chicken/Texas/298313/04 [TX/04]) was not virulent for experimentally inoculated chickens. The hemagglutinin (HA) gene of the TX/04 isolate was similar in sequence to A/chicken/Texas/167280-4/02 (TX/02), a low-pathogenicity AIV isolate recovered from chickens in Texas in 2002. However, the TX/04 isolate had one additional basic amino acid at the HA cleavage site, which could be attributed to a single point mutation. The TX/04 isolate was similar in sequence to TX/02 isolate in several internal genes (NP, M, and NS), but some genes (PA, PB1, and PB2) had sequence of a clearly different origin. The TX/04 isolate also had a stalk deletion in the NA gene, characteristic of a chicken-adapted AIV. By analyzing viruses constructed by in vitro mutagenesis followed by reverse genetics, we found that the pathogenicity of the TX/04 virus could be increased in vitro and in vivo by the insertion of an additional basic amino acid at the HA cleavage site and not by the loss of a glycosylation site near the cleavage site. Our study provides the genetic and biologic characteristics of the TX/04 isolate, which highlight the complexity of the polygenic nature of the virulence of influenza viruses.

scholarly journals Antibody responses to avian influenza viruses in wild birds broaden with age

2016 ◽  
Vol 283 (1845) ◽  
pp. 20162159 ◽  
Author(s):  
Sarah C. Hill ◽  
Ruth J. Manvell ◽  
Bodo Schulenburg ◽  
Wendy Shell ◽  
Paul S. Wikramaratna ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Haemagglutination Inhibition ◽  
Wild Birds ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Immune Recognition ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Age Related ◽  
Pathogenic H5n1

For viruses such as avian influenza, immunity within a host population can drive the emergence of new strains by selecting for viruses with novel antigens that avoid immune recognition. The accumulation of acquired immunity with age is hypothesized to affect how influenza viruses emerge and spread in species of different lifespans. Despite its importance for understanding the behaviour of avian influenza viruses, little is known about age-related accumulation of immunity in the virus's primary reservoir, wild birds. To address this, we studied the age structure of immune responses to avian influenza virus in a wild swan population ( Cygnus olor ), before and after the population experienced an outbreak of highly pathogenic H5N1 avian influenza in 2008. We performed haemagglutination inhibition assays on sampled sera for five avian influenza strains and show that breadth of response accumulates with age. The observed age-related distribution of antibody responses to avian influenza strains may explain the age-dependent mortality observed during the highly pathogenic H5N1 outbreak. Age structures and species lifespan are probably important determinants of viral epidemiology and virulence in birds.

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 Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Bryan S. Kaplan ◽  
Marion Russier ◽  
Trushar Jeevan ◽  
Bindumadhav Marathe ◽  
Elena A. Govorkova ◽  
...  
Keyword(s):  
North America ◽  
Avian Influenza ◽  
North American ◽  
Influenza Viruses ◽  
Morbidity And Mortality ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
The North ◽  
Domestic Poultry ◽  
The Impact

ABSTRACT Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses. Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.

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