The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice

2019 ◽  
Vol 67 (2) ◽  
pp. 758-768
Author(s):  
Xiaoli Hao ◽  
Jiao Hu ◽  
Xiaoquan Wang ◽  
Min Gu ◽  
Jiongjiong Wang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
H9n2 Virus ◽  
Avian Influenza Viruses

scholarly journals Contribution of Segment 3 to the Acquisition of Virulence in Contemporary H9N2 Avian Influenza Viruses

2020 ◽  
Vol 94 (20) ◽  
Author(s):  
Anabel L. Clements ◽  
Joshua E. Sealy ◽  
Thomas P. Peacock ◽  
Jean-Remy Sadeyen ◽  
Saira Hussain ◽  
...  
Keyword(s):  
Middle East ◽  
Avian Influenza ◽  
Mortality Rates ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Morbidity And Mortality ◽  
Single Amino Acid ◽  
Economic Damage ◽  
Poultry Production ◽  
Avian Influenza Viruses

ABSTRACT H9N2 avian influenza viruses (AIVs) circulate in poultry throughout much of Asia, the Middle East, and Africa. These viruses cause huge economic damage to poultry production systems and pose a zoonotic threat both in their own right and in the generation of novel zoonotic viruses, for example, H7N9. In recent years, it has been observed that H9N2 viruses have further adapted to gallinaceous poultry, becoming more highly transmissible and causing higher morbidity and mortality. Here, we investigate the molecular basis for this increased virulence, comparing a virus from the 1990s and a contemporary field strain. The modern virus replicated to higher titers in various systems, and this difference mapped to a single amino acid polymorphism at position 26 of the endonuclease domain shared by the PA and PA-X proteins. This change was responsible for increased replication and higher morbidity and mortality rates along with extended tissue tropism seen in chickens. Although the PA K26E change correlated with increased host cell shutoff activity of the PA-X protein in vitro, it could not be overridden by frameshift site mutations that block PA-X expression and therefore increased PA-X activity could not explain the differences in replication phenotype. Instead, this indicates that these differences are due to subtle effects on PA function. This work gives insight into the ongoing evolution and poultry adaptation of H9N2 and other avian influenza viruses and helps us understand the striking morbidity and mortality rates in the field, as well as the rapidly expanding geographical range seen in these viruses. IMPORTANCE Avian influenza viruses, such as H9N2, cause huge economic damage to poultry production worldwide and are additionally considered potential pandemic threats. Understanding how these viruses evolve in their natural hosts is key to effective control strategies. In the Middle East and South Asia, an older H9N2 virus strain has been replaced by a new reassortant strain with greater fitness. Here, we take representative viruses and investigate the genetic basis for this “fitness.” A single mutation in the virus was responsible for greater fitness, enabling high growth of the contemporary H9N2 virus in cells, as well as in chickens. The genetic mutation that modulates this change is within the viral PA protein, a part of the virus polymerase gene that contributes to viral replication as well as to virus accessory functions—however, we find that the fitness effect is specifically due to changes in the protein polymerase activity.

scholarly journals The PB2 and M genes of genotype S H9N2 virus contribute to the enhanced fitness of H5Nx and H7N9 avian influenza viruses in chickens

Virology ◽  
2019 ◽  
Vol 535 ◽  
pp. 218-226 ◽  
Author(s):  
Xiaoli Hao ◽  
Xiaoquan Wang ◽  
Jiao Hu ◽  
Min Gu ◽  
Jiongjiong Wang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Avian Influenza Viruses

Differential Viral Fitness Between H1N1 and H3N8 Avian Influenza Viruses Isolated from Mallards (Anas platyrhynchos)

2016 ◽  
Vol 60 (1s) ◽  
pp. 406-406
Author(s):  
Helena Lage Ferreira ◽  
Didier Vangeluwe ◽  
Steven Van Borm ◽  
Olivier Poncin ◽  
Nathalie Dumont ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Anas Platyrhynchos ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Avian Influenza Viruses

scholarly journals Novel reassortant of H9N2 avian influenza viruses isolated from chickens and quails in Egypt

2021 ◽  
pp. 2142-2149
Author(s):  
Moataz Elsayed ◽  
AbdelSatar Arafa ◽  
Shahira Abdelwahab ◽  
Amro Hashish ◽  
Ahmed Youssef
Keyword(s):  
Avian Influenza ◽  
Influenza Pandemic ◽  
Phylogenetic Analyses ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Avian Influenza Viruses ◽  
Genetic Changes ◽  
Genome Variability ◽  
Commercial Chicken ◽  
Amino Acid Mutations

Background and Aim: Poultry infections with H9N2 avian influenza viruses (AIVs) are endemic in Egypt. This study determined the genetic changes in the sequences of H9N2 AIVs isolated from chicken and quails in Egypt, including determining genetic reassortment and detecting the main genetic changes in hemagglutinin (HA) and neuraminidase (NA) genes. Materials and Methods: Swab samples were collected from chicken and quails, examined through reverse transcription-polymerase chain reaction, and AIVs from positive samples were isolated in embryonated chicken eggs. Complete genome sequencing and phylogenetic analyses were conducted for two H9N2 AIV isolates, and sequences of HA and NA gene segments were analyzed in another two isolates. Results: A novel reassortant virus was identified from a commercial chicken flock (A/chicken/Egypt/374V/2016) and quails from a live bird market (A/quail/Egypt/1253V/2016). The reassortant viruses acquired four genome segments from the classic Egyptian H9N2 viruses (HA, NA, NP, and M) and four segments from Eurasian AIVs (PB2, PB1, PA, and NS). Many genetic changes have been demonstrated in HA and NA genes. The isolated novel reassortant H9N2 virus from quails showed amino acid mutations in the antigenic sites on the globular head of the mature HA monomer matched with the parent Egyptian H9N2 virus. Conclusion: This work described the genetic characterization of a novel reassortment of the H9N2 virus in Egypt. The emergence of new reassorted AIV viruses and genome variability raises the concern of an influenza pandemic with zoonotic potentials.

scholarly journals Bioaerosol Sampling at a Live Animal Market in Kunshan, China: A Noninvasive Approach for Detecting Emergent Viruses

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Xinye Wang ◽  
Emily S Bailey ◽  
Xian Qi ◽  
Huiyan Yu ◽  
Changjun Bao ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Molecular Evidence ◽  
Avian Influenza Viruses ◽  
Live Animal ◽  
Live Bird Market ◽  
Live Bird

From October to December 2018, periodic bioaerosol sampling was conducted at a live bird market in Kunshan, China. Sixty-six (55%) of 120 samples had molecular evidence of avian influenza viruses. Four yielded live H9N2 virus after egg culture.

scholarly journals Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic Characteristics

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Thomas P. Peacock ◽  
Donald J. Benton ◽  
Joe James ◽  
Jean-Remy Sadeyen ◽  
Pengxiang Chang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Receptor Binding ◽  
Immune Escape ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Antigenic Drift ◽  
Zoonotic Infection ◽  
Avian Influenza Viruses ◽  
The Impact

ABSTRACT H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa, where they pose a threat to human health as both zoonotic agents and potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions; however, vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza virus antigen hemagglutinin (HA). Using selection with HA-specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBSs). Here we analyzed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that mutant viruses with RBS deletions are able to escape polyclonal antiserum binding and are able to infect and be transmitted between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells; however, the mutant HAs also displayed reduced pH and thermal stability. In summary, we infer that variant influenza viruses with deletions in the 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude that these viruses are unlikely to be transmitted from human to human by the airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence. IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden; however, influenza viruses are able to rapidly evolve to escape immune pressure in a process known as “antigenic drift.” Previously, we experimentally generated antigenic-drift variants in the laboratory, and here, we test our “drifted” viruses to assess their zoonotic infection characteristics and transmissibility in chickens. We found that the drifted viruses were able to infect and be transmitted between chickens and showed increased binding to human-like receptors. However, the drift mutant viruses displayed reduced stability, and we predict that they are unlikely to be transmitted from human to human and cause an influenza pandemic. These results demonstrate the complex relationship between antigenic drift and the potential of avian influenza viruses to infect humans.

scholarly journals Genetic Characteristics and Pathogenicity Analysis in Chickens and Mice of Three H9N2 Avian Influenza Viruses

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1127 ◽  
Author(s):  
Yafen Song ◽  
Yong Zhang ◽  
Ling Chen ◽  
Bing Zhang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Avian Influenza ◽  
Animal Studies ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Post Inoculation ◽  
Avian Influenza Viruses ◽  
Genetic Characteristics ◽  
H9n2 Avian Influenza Virus ◽  
Virus Surveillance

H9N2 avian influenza is a remarkable disease that has circulated in domestic poultry in large regions of China and posed a serious threat to the poultry industry. The H9N2 virus can not only infect mammals directly, but also provide gene segments to generate novel, but lethal human reassortants. Therefore, it is important to study the evolution, pathogenicity, and transmission of the H9N2 virus. In this study, three H9N2 viruses isolated from chickens in different layer farms were identified. Phylogenetic analysis revealed that these H9N2 viruses were all multiple genotype reassortants, with genes originating from Y280-like, F/98-like, and G1-like viruses. Animal studies indicated that the AV1535 and AV1548 viruses replicated efficiently in the lungs, tracheas, spleens, kidneys, and brains of chickens; the viruses shed for at least 11 days post-inoculation (DPI) and were transmitted efficiently among contact chickens. The AV1534 virus replicated poorly in chickens, shed for 7 DPI, and were not transmitted efficiently among contact chickens. The AV1534 virus replicated well in mice lungs and caused about 2% weight loss. The AV1535 and AV1548 viruses were not able to replicate in the lungs of mice. Our results indicate that we should pay attention to H9N2 avian influenza virus surveillance in poultry and changes in the pathogenicity of them to mammals.

scholarly journals Characterizing the Core Internal Gene Pool of H9N2 Responsible for Continuous Reassortment With Other Influenza A Viruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Haoyi Yang ◽  
Mingda Hu ◽  
Boqian Wang ◽  
Yuan Jin ◽  
Xingfei Gong ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Geographic Distribution ◽  
Phylogenetic Relationships ◽  
Gene Pool ◽  
Feature Vector ◽  
Core Gene ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Avian Influenza Viruses ◽  
The Core

Reassortment among avian influenza viruses is the main source of novel avian influenza virus subtypes. Studies have shown that the H9N2 virus often donates internal segments to generate novel reassortant avian influenza viruses, acting as a reassortment template. However, the characteristics of the internal pattern of reassortment remain unclear. In this article, we first defined the core gene pool of the internal segments of the H9N2 virus that provide templates for reassortment. We used genetic distance and sequence similarity to define typical clusters in the core gene pool. Then, we analyzed the phylogenetic relationships, feature vector distances, geographic distributions and mutation sites of strains related to the core gene pool. Strains in the same typical clusters have close phylogenetic relationships and feature vector distances. We also found that these typical clusters can be divided into three categories according to their main geographic distribution area. Furthermore, typical clusters in the same geographic area contain some common mutation patterns. Our results suggest that typical clusters in the core gene pool affect the reassortment events of the H9N2 virus in many respects, such as geographic distribution and amino acid mutation sites.

scholarly journals Contribution of segment 3 to the acquisition of virulence in contemporary H9N2 avian influenza viruses

2020 ◽  
Author(s):  
Anabel L. Clements ◽  
Joshua E. Sealy ◽  
Thomas P. Peacock ◽  
Jean-Remy Sadeyen ◽  
Saira Hussain ◽  
...  
Keyword(s):  
Middle East ◽  
Avian Influenza ◽  
Influenza Viruses ◽  
H9n2 Virus ◽  
Morbidity And Mortality ◽  
Single Amino Acid ◽  
Effective Control ◽  
Economic Damage ◽  
Poultry Production ◽  
Avian Influenza Viruses

AbstractH9N2 avian influenza viruses circulate in poultry throughout much of Asia, the Middle East and Africa. These viruses cause huge economic damage to poultry production systems and pose a zoonotic threat both in their own right as well as in the generation of novel zoonotic viruses, for example H7N9. In recent years it has been observed that H9N2 viruses have further adapted to poultry, becoming more highly transmissible and causing higher morbidity and mortality. Here, we investigate the molecular basis for this increased virulence, comparing a virus from the 1990s and a contemporary field strain. The modern virus replicated to higher titres in various systems and this difference mapped to a single amino acid polymorphism at position 26 of the endonuclease domain shared by the PA and PA-X proteins. This change was responsible for the virulent phenotype and extended tissue tropism seen in chickens. Although the PA K26E change correlated with increased host cell shutoff activity of the PA-X protein in vitro, it could not be overridden by frameshift site mutations that block PA-X expression and therefore increased PA-X activity could not explain the differences in replication phenotype. Instead, this indicates these differences are due to subtle effects on PA function. This work gives insight into the ongoing evolution and poultry adaptation of H9N2 and other avian influenza viruses and helps us understand the soaring morbidity and mortality rates in the field, as well as rapidly expanding geographical range seen in these viruses.Author SummaryAvian influenza viruses, such as H9N2, cause huge economic damage to poultry production worldwide and are additionally considered potential pandemic threats. Understanding how these viruses evolve in their natural hosts is key to effective control strategies. In the Middle East and South Asia an older H9N2 virus strain has been replaced by a new reassortant strain with greater fitness. Here we take representative viruses and investigate the genetic basis for this ‘fitness’. A single mutation in the virus was responsible for greater fitness, enabling high growth of the contemporary H9N2 virus in cells, as well as in chickens. The genetic mutation that modulates this change is within the viral PA protein, a part of the virus polymerase gene that contributes in viral replication as well as contribute in the virus accessory functions – however we find that the fitness effect is specifically due to changes in the protein polymerase activity.

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