Detection of avian influenza virus: a comparative study of the in silico and in vitro performances of current RT-qPCR assays

Human infections with the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threatens public health. The susceptibility of HPAIVs to baloxavir acid (BXA), which is a new class of inhibitor for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but has not yet been characterized fully. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants in vitro was assessed. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested to those of seasonal and other zoonotic strains. BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate; A/Hong Kong/483/1997 (H5N1) strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, followed by prevention of acute lung inflammation and improvement of mortality compared with oseltamivir phosphate (OSP). Furthermore, combination treatments with BXM and OSP, using a 48-hour delayed treatment model showed a more potent effect on viral replication in organs, accompanied by improved survival compared to BXM or OSP monotherapy. From each test, no resistant virus (e.g., I38T in the PA) emerged in any BXM-treated mouse. These results therefore support the conclusion that BXM has potent antiviral efficacy against H5 HPAIV infections.

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Immunology of avian influenza virus: a review

Developmental & Comparative Immunology ◽

10.1016/s0145-305x(99)00078-6 ◽

2000 ◽

Vol 24 (2-3) ◽

pp. 269-283 ◽

Cited By ~ 129

Author(s):

D Suarez

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Influenza Virus A

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Genetic Characterization of Avian Influenza A (H11N9) Virus Isolated from Mandarin Ducks in South Korea in 2018

Viruses ◽

10.3390/v12020203 ◽

2020 ◽

Vol 12 (2) ◽

pp. 203

Author(s):

Hien Thi Tuong ◽

Ngoc Minh Nguyen ◽

Haan Woo Sung ◽

Hyun Park ◽

Seon-Ju Yeo

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

South Korea ◽

Avian Influenza Virus ◽

Influenza A ◽

Sequence Similarity ◽

Basic Amino Acid ◽

Wild Birds

In July 2018, a novel avian influenza virus (A/Mandarin duck/South Korea/KNU18-12/2018(H11N9)) was isolated from Mandarin ducks in South Korea. Phylogenetic and molecular analyses were conducted to characterize the genetic origins of the H11N9 strain. Phylogenetic analysis indicated that eight gene segments of strain H11N9 belonged to the Eurasian lineages. Analysis of nucleotide sequence similarity of both the hemagglutinin (HA) and neuraminidase (NA) genes revealed the highest homology with A/duck/Kagoshima/KU57/2014 (H11N9), showing 97.70% and 98.00% nucleotide identities, respectively. Additionally, internal genes showed homology higher than 98% compared to those of other isolates derived from duck and wild birds. Both the polymerase acidic (PA) and polymerase basic 1 (PB1) genes were close to the H5N3 strain isolated in China; whereas, other internal genes were closely related to that of avian influenza virus in Japan. A single basic amino acid at the HA cleavage site (PAIASR↓GLF), the lack of a five-amino acid deletion (residue 69–73) in the stalk region of the NA gene, and E627 in the polymerase basic 2 (PB2) gene indicated that the A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) isolate was a typical low-pathogenicity avian influenza. In vitro viral replication of H11N9 showed a lower titer than H1N1 and higher than H9N2. In mice, H11N9 showed lower adaptation than H1N1. The novel A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) isolate may have resulted from an unknown reassortment through the import of multiple wild birds in Japan and Korea in approximately 2016–2017, evolving to produce a different H11N9 compared to the previous H11N9 in Korea (2016). Further reassortment events of this virus occurred in PB1 and PA in China-derived strains. These results indicate that Japanese- and Chinese-derived avian influenza contributes to the genetic diversity of A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) in Korea.

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Productive infection in the murine central nervous system with avian influenza virus A (H5N1) after intranasal inoculation

Acta Neuropathologica ◽

10.1007/s00401-004-0909-0 ◽

2004 ◽

Vol 108 (6) ◽

pp. 485-492 ◽

Cited By ~ 31

Author(s):

Takuya Iwasaki ◽

Shigeyuki Itamura ◽

Hidekazu Nishimura ◽

Yuko Sato ◽

Masato Tashiro ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Productive Infection ◽

Intranasal Inoculation ◽

Influenza Virus A

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The NS Segment of an H5N1 Highly Pathogenic Avian Influenza Virus (HPAIV) Is Sufficient To Alter Replication Efficiency, Cell Tropism, and Host Range of an H7N1 HPAIV

Journal of Virology ◽

10.1128/jvi.01668-09 ◽

2009 ◽

Vol 84 (4) ◽

pp. 2122-2133 ◽

Cited By ~ 57

Author(s):

Wenjun Ma ◽

Dominique Brenner ◽

Zhongfang Wang ◽

Bianca Dauber ◽

Christina Ehrhardt ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Host Range ◽

Highly Pathogenic Avian Influenza ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza ◽

Primary Mouse ◽

Pathogenic Avian Influenza Virus

ABSTRACT A reassortant avian influenza virus (designated FPV NS GD), carrying the NS-segment of the highly pathogenic avian influenza virus (HPAIV) strain A/Goose/Guangdong/1/96 (GD; H5N1) in the genetic background of the HPAIV strain A/FPV/Rostock/34 (FPV; H7N1), was rescued by reverse genetics. Remarkably, in contrast to the recombinant wild-type FPV (rFPV), the reassortant virus was able to replicate more efficiently in different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, FPV NS GD caused disease and death in experimentally infected mice and was detected in mouse lungs; in contrast, rFPV was not able to replicate in mice effectively. These results indicated an altered host range and increased virulence. Furthermore FPV NS GD showed pronounced pathogenicity in chicken embryos. In an attempt to define the molecular basis for the apparent differences, we determined that NS1 proteins of the H5N1 and H7N1 strains bound the antiviral kinase PKR and the F2F3 domain of cleavage and polyadenylation specificity factor 30 (CPSF30) with comparable efficiencies in vitro. However, FPV NS GD infection resulted in (i) increased expression of NS1, (ii) faster and stronger PKR inhibition, and (iii) stronger beta interferon promoter inhibition than rFPV. Taken together, the results shed further light on the importance of the NS segment of an H5N1 strain for viral replication, molecular pathogenicity, and host range of HPAIVs and the possible consequences of a reassortment between naturally occurring H7 and H5 type HPAIVs.

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