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

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1066 ◽  
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.

scholarly journals Will China’s H7N9 Control Strategy Continue to Be Effective?

2019 ◽  
Vol 6 (6) ◽  
Author(s):  
Guo-Lin Wang ◽  
Gregory C Gray ◽  
Ji-Ming Chen ◽  
Mai-Juan Ma
Keyword(s):  
Virus Infection ◽  
Avian Influenza ◽  
Control Strategy ◽  
Influenza A ◽  
Human Infection ◽  
H7n9 Virus ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Live Poultry ◽  
Live Poultry Markets

Abstract Since the first outbreak of avian influenza A(H7N9) virus in China in early 2013, several interventions to control the transmission of H7N9 virus from poultry to humans have been implemented. Temporarily closing live poultry markets reduced the risk of human infection to an extent, but it did not prevent the spread of the H7N9 virus among poultry, and this spread eventually led to more human cases. Nevertheless, the mass vaccination of poultry after September 2017 has been highly effective in preventing the H7N9 virus infection in both poultry and humans. In light of the emergence of highly pathogenic H7N9 and H7N2 viruses in unimmunized ducks, vaccination among poultry, especially for ducks, should be accompanied with continued surveillance of H7N9 variants and other avian influenza A viruses that could signal a heightened pandemic risk.

scholarly journals The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus

2021 ◽  
Author(s):  
Xiao-Xin Wu ◽  
Song-Jia Tang ◽  
Shu-Hao Yao ◽  
Yu-Qin Zhou ◽  
Lan-Lan Xiao ◽  
...  
Keyword(s):  
Virus Infection ◽  
Post Infection ◽  
Lung Infection ◽  
Multiple Organ ◽  
Organ Injury ◽  
H7n9 Virus ◽  
Pathological Changes ◽  
Highly Pathogenic ◽  
Viral Distribution ◽  
Influenza H7n9 Virus

Abstract Background The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. Methods Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. Results The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. Conclusion Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

scholarly journals The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiao-Xin Wu ◽  
Song-Jia Tang ◽  
Shu-Hao Yao ◽  
Yu-Qin Zhou ◽  
Lan-Lan Xiao ◽  
...  
Keyword(s):  
Virus Infection ◽  
Post Infection ◽  
Lung Infection ◽  
Multiple Organ ◽  
Organ Injury ◽  
H7n9 Virus ◽  
Pathological Changes ◽  
Highly Pathogenic ◽  
Viral Distribution ◽  
Influenza H7n9 Virus

Abstract Background The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. Methods Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. Results The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. Conclusion Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

scholarly journals New hemagglutinin dual-receptor-binding pattern of a human-infecting influenza A (H7N9) virus isolated after fifth epidemic wave

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Lei Guo ◽  
Nan Li ◽  
Wenlong Li ◽  
Jienan Zhou ◽  
Ruotong Ning ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Influenza A ◽  
Human Infection ◽  
Binding Property ◽  
H7n9 Virus ◽  
Receptor Binding Site ◽  
Highly Pathogenic ◽  
Influenza H7n9 Virus ◽  
Epidemic Wave ◽  
Human Receptor

Abstract Since 2013, influenza H7N9 virus has caused five epidemic waves of human infection. The virus evolved from low pathogenic to highly pathogenic in wave 5, 2017, while the prevalence of host receptor-binding tropism in human-infecting viruses maintained dual-receptor-binding property with preference for avian receptor. A human-infecting H7N9 virus was isolated after the fifth epidemic wave and possessed an avian and human dual-receptor specificity, with a moderately higher affinity for human receptor binding. A V186I (H3 numbering) substitution in the receptor-binding site of the hemagglutinin (HA) molecule is responsible for the alteration of the dual-receptor-binding tropism. Viral strains which contain I186 amino acid of avian- and human-infecting H7N9 viruses were all isolated during or after wave 5, and their HA genes clustered in a same phylogenetic clade together with 2018–9 H7N9 isolates, highlights a new evolutionary path for human adaption of natural H7N9 viruses.

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

2015 ◽  
Vol 14 (11) ◽  
pp. 4511-4523 ◽  
Author(s):  
Philippe François Simon ◽  
Stuart McCorrister ◽  
Pingzhao Hu ◽  
Patrick Chong ◽  
Alex Silaghi ◽  
...  
Keyword(s):  
Influenza A ◽  
Host Responses ◽  
Pandemic H1n1 ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
H7n9 Influenza ◽  
Pathogenic H5n1

scholarly journals Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic

2021 ◽  
Author(s):  
William J. Liu ◽  
Haixia Xiao ◽  
Lianpan Dai ◽  
Di Liu ◽  
Jianjun Chen ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
New Technologies ◽  
Vaccine Development ◽  
H7n9 Virus ◽  
Emerging Viruses ◽  
Highly Pathogenic ◽  
Cell Responses ◽  
Live Poultry ◽  
H7n9 Influenza

AbstractThe avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

scholarly journals The Viral Distribution and Pathological Characteristics of BALB/c Mice Infected With Highly Pathogenic Influenza H7N9 Virus

2021 ◽  
Author(s):  
Xiao-Xin Wu ◽  
Song-Jia Tang ◽  
Shu-Hao Yao ◽  
Yu-Qin Zhou ◽  
Lan-Lan Xiao ◽  
...  
Keyword(s):  
Virus Infection ◽  
Lung Infection ◽  
Multiple Organ ◽  
Organ Injury ◽  
H7n9 Virus ◽  
Pathological Changes ◽  
Weight Changes ◽  
Highly Pathogenic ◽  
Viral Distribution ◽  
Influenza H7n9 Virus

Abstract Background: The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus.Methods: The mice were infected with A/Guangdong/GZ8H002/2017(H7N9) virus via nasal inoculation. Some mice were killed at 2, 3, and 7 days after infection. The other mice were used to observe their illness status and weight changes. The characteristics of viral invasion were analysed using reverse transcription polymerase chain reaction and viral isolation. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry.Results: The weight of mice infected with A/Guangdong/GZ8H002/2017(H7N9) virus increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days by up to 20%. All the mice had died by the 8th day after infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day after infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day after infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high.Conclusion: Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

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

2017 ◽  
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.

Inhibition of Novel Reassortant Avian Influenza H7N9 Virus Infection in vitro with Three Antiviral Drugs, Oseltamivir, Peramivir and Favipiravir

2014 ◽  
Vol 23 (6) ◽  
pp. 237-240 ◽  
Author(s):  
Rui-Yuan Cao ◽  
Jun-Hai Xiao ◽  
Bin Cao ◽  
Song Li ◽  
Yohichi Kumaki ◽  
...  
Keyword(s):  
Virus Infection ◽  
Avian Influenza ◽  
Influenza A ◽  
Antiviral Agents ◽  
H7n9 Virus ◽  
Avian Origin ◽  
Influenza H7n9 Virus ◽  
Virus Strains ◽  
Respiratory Specimens

Background: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from three patients and was identified as H7N9 in China. Antiviral agents are required to treat patients with avian influenza H7N9 virus infection. Methods: In this study, we assessed the antiviral potential of oseltamivir, peramivir, favipiravir (T-705), amantadine and rimantadine against novel reassortant avian-origin influenza H7N9 virus in vitro. Results: All three avian influenza H7N9 virus strains were sensitive to oseltamivir, peramivir and favipiravir (T-705), but resistant to amantadine and rimantadine. Conclusions: Our data show a pattern of antiviral sensitivity for this novel H7N9 strain of influenza that suggests the compounds oseltamivir, peramivir and favipiravir should be useful for therapy.

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