scholarly journals Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Dongming Zhao ◽  
Libin Liang ◽  
Shuai Wang ◽  
Tomomi Nakao ◽  
Yanbing Li ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Single Amino Acid ◽  
Effective Control ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n1 Influenza ◽  
Hpai H5n1 ◽  
Ha Protein

ABSTRACT The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. In this study, we explored the molecular determinants and potential mechanism for this difference in virulence. By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals. IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice.

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 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 Genetic evolution and transmission dynamics of clade 2.3.2.1a highly pathogenic avian influenza A/H5N1 viruses in Bangladesh

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Jung-Hoon Kwon ◽  
Dong-Hun Lee ◽  
Miria Ferreira Criado ◽  
Lindsay Killmaster ◽  
Md Zulfekar Ali ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Effective Control ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
History Of ◽  
Genetic Sequences

Abstract Asian lineage A/H5N1 highly pathogenic avian influenza viruses (HPAIVs) have been responsible for continuous outbreaks in Bangladesh since 2007. Although clades 2.2.2 and 2.3.4.2 HPAIVs have disappeared since poultry vaccination was introduced in 2012, clade 2.3.2.1a viruses have continued to be detected in Bangladesh. In this study, we identified A/H9N2 (n = 15), A/H5N1 (n = 19), and A/H5N1-A/H9N2 (n = 18) mixed viruses from live bird markets, chicken farms, and wild house crows (Corvus splendens) in Bangladesh from 2016 to 2018. We analyzed the genetic sequences of the H5 HPAIVs, to better understand the evolutionary history of clade 2.3.2.1a viruses in Bangladesh. Although seven HA genetic subgroups (B1–B7) and six genotypes (G1, G1.1, G1.2, G2, G2.1, and G2.2) have been identified in Bangladesh, only subgroup B7 and genotypes G2, G2.1, and G2.2 were detected after 2016. The replacement of G1 genotype by G2 in Bangladesh was possibly due to vaccination and viral competition in duck populations. Initially, genetic diversity decreased after introduction of vaccination in 2012, but in 2015, genetic diversity increased and was associated with the emergence of genotype G2. Our phylodynamic analysis suggests that domestic Anseriformes, including ducks and geese, may have played a major role in persistence, spread, evolution, and genotype replacement of clade 2.3.2.1a HPAIVs in Bangladesh. Thus, improvements in biosecurity and monitoring of domestic Anseriformes are needed for more effective control of HPAI in Bangladesh.

The East Jakarta Project: surveillance for highly pathogenic avian influenza A(H5N1) and seasonal influenza viruses in patients seeking care for respiratory disease, Jakarta, Indonesia, October 2011–September 2012

2015 ◽  
Vol 143 (16) ◽  
pp. 3394-3404 ◽  
Author(s):  
A. D. STORMS ◽  
R. KUSRIASTUTI ◽  
S. MISRIYAH ◽  
C. Y. PRAPTININGSIH ◽  
M. AMALYA ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Respiratory Disease ◽  
H5n1 Virus ◽  
Seasonal Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1

SUMMARYIndonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription–polymerase chain reaction. During October 2011–September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December–May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season.

scholarly journals Isolation of a Novel Reassortant Highly Pathogenic Avian Influenza (H5N2) Virus in Egypt

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 565 ◽  
Author(s):  
Naglaa M. Hagag ◽  
Ahmed M. Erfan ◽  
Mohamed El-Husseiny ◽  
Azhar G. Shalaby ◽  
Mohamed A. Saif ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n2 Virus ◽  
Domestic Poultry ◽  
Hpai H5n1 ◽  
Avian Influenza H9n2

Highly pathogenic avian influenza (HPAI) H5N1 and H5N8 have become endemic among domestic poultry in Egypt since 2006 and 2016, respectively. In parallel, the low pathogenic avian influenza H9N2 virus has been endemic since 2010. Despite the continuous circulation of these subtypes for several years, no natural reassortant has been detected so far among the domestic poultry population in Egypt. In this study, the HPAI (H5N2) virus was isolated from a commercial duck farm, giving evidence of the emergence of the first natural reassortment event in domestic poultry in Egypt. The virus was derived as a result of genetic reassortment between avian influenza viruses of H5N8 and H9N2 subtypes circulating in Egypt. The exchange of the neuraminidase segment and high number of acquired mutations might be associated with an alteration in the biological propensities of this virus.

scholarly journals Molecular characterization and epidemiology of the highly pathogenic avian influenza H5N1 in Nigeria

2008 ◽  
Vol 137 (4) ◽  
pp. 456-463 ◽  
Author(s):  
F. O. FASINA ◽  
S. P. R. BISSCHOP ◽  
T. M. JOANNIS ◽  
L. H. LOMBIN ◽  
C. ABOLNIK
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Control Measures ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1 ◽  
Monospecific Antisera ◽  
Influenza H5n1 ◽  
Live Bird

SUMMARYAvian influenza caused infection and spread throughout Nigeria in 2006. Carcass samples (lung, liver, spleen, heart, trachea and intestine) from the different regions of Nigeria were processed for virus isolation. Infective allantoic fluids were tested for avian influenza viruses (AIV) and Newcastle disease virus using monospecific antisera. Thirty-five isolates were generated and characterized molecularly using the haemagglutinin gene. The molecular analysis indicated that different sublineages of the highly pathogenic avian influenza (HPAI) H5N1 viruses spread throughout Nigeria. We compared the Nigerian isolates with others from Africa and results indicated close similarities between isolates from West Africa and Sudan. Some of the analysed viruses showed genetic drift, and the implications of these for future epidemiology and ecology of avian influenza in Africa require further evaluation. The spread of primary outbreaks was strongly linked to trade (legal and illegal), live bird markets, inappropriate disposal, and poorly implemented control measures. No strong correlation existed between wild birds and HPAI H5N1 in Nigeria.

scholarly journals SUMOylation of matrix protein M1 and filamentous morphology collectively contribute to the replication and virulence of highly pathogenic H5N1 avian influenza viruses in mammals

2021 ◽  
Author(s):  
Jing Guo ◽  
Jianing Chen ◽  
Yuanyuan Li ◽  
Yanbing Li ◽  
Guohua Deng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Matrix Protein ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n1 Influenza ◽  
Matrix Protein M1

The matrix protein (M1) of influenza A virus plays an important role in replication, assembly, and budding. A previous study found that aspartic acid (D) at position 30 and alanine (A) at position 215 of M1 contribute to the high pathogenicity of H5N1 viruses in mice, and double mutations of D to asparagine (N) at position 30 (D30N) and A to threonine (T) at position 215 (A215T) in M1 dramatically attenuate H5N1 viruses in mice. However, the underlying mechanisms by which these M1 mutations attenuate the virulence of H5N1 viruses are unknown. Here, we found that the amino acid mutation A215T eliminates the SUMOylation of M1 by reducing its interaction with the host SUMO1 protein, significantly reducing the stability of M1, slowing the export of the M1-vRNP complex from the nucleus to the cytoplasm, and reducing viral replication in MDCK cells. We further found that the D30N mutation in M1 alters the shape of progeny viruses from filamentous to spherical virions. Our findings reveal an essential role for M1 215A SUMOylation and M1 30D-related filamentous morphology in the pathogenesis of avian influenza viruses, which could be targeted in novel antiviral drug designs. Importance Identification of the pathogenic mechanism of highly pathogenic avian influenza viruses in mammals is helpful to develop novel anti-influenza virus strategies. Two amino acid mutations (D30N and A215T) in M1 were found to collectively attenuate H5N1 influenza viruses in mice, but the underlying mechanism remained unknown. This study found that the A215T mutation significantly decreases the SUMOylation of M1, which in turn attenuates the replication of H5N1 virus in mammalian cells. The D30N mutation in M1 was found to change the virion shape from filamentous to spherical. These findings are important for understanding the molecular mechanism of virulence of highly pathogenic avian influenza viruses in mammals.

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.

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