Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains

Clinical studies showed that a single mutation, I117V, develops severe resistance to oseltamivir, the first orally active influenza A neuraminidase inhibitor, in highly pathogenic H5N1 influenza A viruses.

Download Full-text

Genetic versus antigenic differences among highly pathogenic H5N1 avian influenza A viruses: Consequences for vaccine strain selection

Virology ◽

10.1016/j.virol.2017.01.012 ◽

2017 ◽

Vol 503 ◽

pp. 83-93 ◽

Cited By ~ 16

Author(s):

Ben Peeters ◽

Sylvia Reemers ◽

Jos Dortmans ◽

Erik de Vries ◽

Mart de Jong ◽

...

Keyword(s):

Avian Influenza ◽

Vaccine Strain ◽

Influenza A ◽

Strain Selection ◽

Influenza A Viruses ◽

Highly Pathogenic ◽

H5n1 Avian Influenza ◽

Pathogenic H5n1

Download Full-text

Apoptotic and Early Innate Immune Responses to PB1-F2 Protein of Influenza A Viruses Belonging to Different Subtypes in Human Lung Epithelial A549 Cells

Advances in Virology ◽

10.1155/2018/5057184 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12

Author(s):

Gunisha Pasricha ◽

Sanjay Mukherjee ◽

Alok K. Chakrabarti

Keyword(s):

Inflammatory Response ◽

Influenza A ◽

H5n1 Virus ◽

A549 Cells ◽

Terminal Region ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Highly Pathogenic ◽

Lung Epithelial ◽

Pathogenic H5n1

PB1-F2 is a multifunctional protein and contributes to the pathogenicity of influenza A viruses. PB1-F2 is known to have strain and cell specific functions. In this study we have investigated the apoptotic and inflammatory responses of PB1-F2 protein from influenza viruses of diverse pathogenicities in A549 lung epithelial cells. Overexpression of PB1-F2 resulted in apoptosis and heightened inflammatory response in A549 cells. Comparison revealed that the response varied with each subtype. PB1-F2 protein from highly pathogenic H5N1 virus induced least apoptosis but maximum inflammatory response. Results indicated that apoptosis was mediated through death receptor ligands TNFα and TRAIL via Caspase 8 activation. Significant induction of cytokines/chemokines CXCL10, CCL5, CCL2, IFNα, and IL-6 was noted in A549 cells transfected with PB1-F2 gene construct of 2008 West Bengal H5N1 virus (H5N1-WB). On the contrary, PB1-F2 construct from 2007 highly pathogenic H5N1 isolate (H5N1-M) with truncated N-terminal region did not evoke as exuberant inflammatory response as the other H5N1-WB with full length PB1-F2, signifying the importance of N-terminal region of PB1-F2. Sequence analysis revealed that PB1-F2 proteins derived from different influenza viruses varied at multiple amino acid positions. The secondary structure prediction showed each of the PB1-F2 proteins had distinct helix-loop-helix structure. Thus, our data substantiate the notion that the contribution of PB1-F2 to influenza pathogenicity is greatly strain specific and involves multiple host factors. This data demonstrates that PB1-F2 protein of influenza A virus, when expressed independently is minimally apoptotic and strongly influences the early host response in A549 cells.

Download Full-text

Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil

Viruses ◽

10.3390/v11111066 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1066 ◽

Cited By ~ 1

Author(s):

Maki Kiso ◽

Seiya Yamayoshi ◽

Yuri Furusawa ◽

Masaki Imai ◽

Yoshihiro Kawaoka

Keyword(s):

Virus Infection ◽

Influenza A ◽

H7n9 Virus ◽

Neuraminidase Inhibitors ◽

Influenza A Viruses ◽

Lethal Challenge ◽

Highly Pathogenic ◽

Limited Efficacy ◽

H7n9 Influenza ◽

Influenza H7n9 Virus

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.

Download Full-text

Molecular evolution, diversity and adaptation of H7N9 influenza A viruses in China

10.1101/155218 ◽

2017 ◽

Cited By ~ 1

Author(s):

Jing Lu ◽

Jayna Raghwani ◽

Jie Wu ◽

Rhys Pryce ◽

Thomas A. Bowden ◽

...

Keyword(s):

Molecular Evolution ◽

Influenza A ◽

Phylogenetic Analyses ◽

High Rate ◽

Influenza A Viruses ◽

Highly Pathogenic ◽

Receptor Recognition ◽

Sequence Reconstruction ◽

Current Outbreak ◽

H7n9 Influenza

SummaryA novel H7N9 avian influenza virus has caused five human epidemics in China since 2013. The substantial increase in prevalence and the emergence of antigenically divergent or highly pathogenic (HP) H7N9 strains during the current outbreak raises concerns about the epizootic-potential of these viruses. Here, we investigate the evolution and adaptation of H7N9 by combining publicly available data with newly generated virus sequences isolated in Guangdong between 2015-2017. Phylogenetic analyses show that currently-circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Using ancestral sequence reconstruction and structural modelling we have identified parallel amino-acid changes on multiple separate lineages. Furthermore, we infer mutations in HA primarily occur at sites involved in receptor-recognition and/or antigenicity. We also identify seven new HP strains, which likely emerged from viruses circulating in eastern Guangdong around March 2016 and is further associated with a high rate of adaptive molecular evolution.

Download Full-text