Higher #virulence of #swine #H1N2 #influenza viruses containing #avian-origin #HA and 2009 #pandemic PA and NP in #pigs and mice (Arch Virol., abstract)

[Source: Archives of Virology, full page: (LINK). Abstract, edited.]

Higher virulence of swine H1N2 influenza viruses containing avian-origin HA and 2009 pandemic PA and NP in pigs and mice

Yunyueng Jang, Taehyun Seo & Sang Heui Seo

Archives of Virology (2020)

 

Abstract

Pigs are capable of harbouring influenza A viruses of human and avian origin in their respiratory tracts and thus act as an important intermediary host to generate novel influenza viruses with pandemic potential by genetic reassortment between the two viruses. Here, we show that two distinct H1N2 swine influenza viruses contain avian-like or classical swine-like hemagglutinins with polymerase acidic (PA) and nucleoprotein (NP) genes from 2009 pandemic H1N1 influenza viruses that were found to be circulating in Korean pigs in 2018. Swine H1N2 influenza virus containing an avian-like hemagglutinin gene had enhanced pathogenicity, causing severe interstitial pneumonia in infected pigs and mice. The mortality rate of mice infected with swine H1N2 influenza virus containing an avian-like hemagglutinin gene was higher by 100% when compared to that of mice infected with swine H1N2 influenza virus harbouring classical swine-like hemagglutinin. Further, chemokines attracting inflammatory cells were strongly induced in lung tissues of pigs and mice infected by swine H1N2 influenza virus containing an avian-like hemagglutinin gene. In conclusion, it is necessary for the well-being of humans and pigs to closely monitor swine influenza viruses containing avian-like hemagglutinin with PA and NP genes from 2009 pandemic H1N1 influenza viruses.

Keywords: Influenza A; Avian Influenza; Swine Influenza; H1N1pdm09; H1N2; Reassortant strain; Pigs; Animal models.

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#Influenza A and B viruses with reduced #baloxavir susceptibility display attenuated in vitro #fitness but retain ferret #transmissibility (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Influenza A and B viruses with reduced baloxavir susceptibility display attenuated in vitro fitness but retain ferret transmissibility

Jeremy C. Jones, Philippe Noriel Q. Pascua, Thomas P. Fabrizio, Bindumadhav M. Marathe, Patrick Seiler, Subrata Barman, Richard J. Webby, Robert G. Webster, and Elena A. Govorkova

PNAS first published March 26, 2020 | DOI: https://doi.org/10.1073/pnas.1916825117

Contributed by Robert G. Webster, February 12, 2020 (sent for review October 2, 2019; reviewed by Rodney S. Daniels and Lieve Naesens)

 

Significance

The emergence of influenza viruses with reduced susceptibility to baloxavir marboxil (BXM) would limit the clinical utility of this novel antiviral. To assess the risk of such resistance emerging, we evaluated influenza A and B viruses carrying BXM-reduced susceptibility substitutions and compared their fitness to that of their drug-susceptible wild-type (I38-WT) counterparts. The 38T/F/M substitutions inhibited activity of the virus PA protein, and two of them (38T/F) hindered virus replication in cells. Even so, 38T/F/M viruses could transmit between ferrets, the gold-standard model for human transmission. These findings argue that there is a risk of transmission of BXM-resistant viruses from treated individuals. Whether such viruses could compete with WT viruses in spreading through the wider untreated community is less clear.

 

Abstract

Baloxavir marboxil (BXM) was approved in 2018 for treating influenza A and B virus infections. It is a first-in-class inhibitor targeting the endonuclease activity of the virus polymerase acidic (PA) protein. Clinical trial data revealed that PA amino acid substitutions at residue 38 (I38T/F/M) reduced BXM potency and caused virus rebound in treated patients, although the fitness characteristics of the mutant viruses were not fully defined. To determine the fitness impact of the I38T/F/M substitutions, we generated recombinant A/California/04/2009 (H1N1)pdm09, A/Texas/71/2017 (H3N2), and B/Brisbane/60/2008 viruses with I38T/F/M and examined drug susceptibility in vitro, enzymatic properties, replication efficiency, and transmissibility in ferrets. Influenza viruses with I38T/F/M substitutions exhibited reduced baloxavir susceptibility, with 38T causing the greatest reduction. The I38T/F/M substitutions impaired PA endonuclease activity as compared to that of wild-type (I38-WT) PA. However, only 38T/F A(H3N2) substitutions had a negative effect on polymerase complex activity. The 38T/F substitutions decreased replication in cells among all viruses, whereas 38M had minimal impact. Despite variable fitness consequences in vitro, all 38T/M viruses disseminated to naive ferrets by contact and airborne transmission, while 38F-containing A(H3N2) and B viruses failed to transmit via the airborne route. Reversion of 38T/F/M to I38-WT was rare among influenza A viruses in this study, suggesting stable retention of 38T/F/M genotypes during these transmission events. BXM reduced susceptibility-associated mutations had variable effects on in vitro fitness of influenza A and B viruses, but the ability of these viruses to transmit in vivo indicates a risk of their spreading from BXM-treated individuals.

influenza – endonuclease inhibitor – baloxavir marboxil – PA protein – I38T substitution

 

Footnotes

1 To whom correspondence may be addressed. Email: Jeremy.jones@stjude.org or robert.webster@stjude.org.

Author contributions: J.C.J., P.N.Q.P., T.P.F., R.J.W., R.G.W., and E.A.G. designed research; J.C.J., P.N.Q.P., B.M.M., and P.S. performed research; J.C.J., P.N.Q.P., T.P.F., and S.B. contributed new reagents/analytic tools; J.C.J., P.N.Q.P., T.P.F., and E.A.G. analyzed data; and J.C.J., P.N.Q.P., R.J.W., R.G.W., and E.A.G. wrote the paper.

Reviewers: R.S.D., The Francis Crick Institute; and L.N., Katholieke Universiteit Leuven.

Competing interest statement: E.A.G. reports receiving consultant fees and travel support from Genentech/Roche for serving on an advisory board. The other authors declare no conflicts of interest.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1916825117/-/DCSupplemental.

Published under the PNAS license.

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Baloxavir.

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#Critical #care #management of adults with community-acquired severe respiratory #viral #infection (Intensive Care Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Critical care management of adults with community-acquired severe respiratory viral infection.

Intensive Care Med. 2020 Feb 10;:

Authors: Arabi YM, Fowler R, Hayden FG

 

Abstract

With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17-53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.

PMID: 32040667 [PubMed – as supplied by publisher]

Keywords: Coronavirus; Influenza A; RSV; Antivirals; Antibiotics; COX-2-inhibitors; Statins.

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Detection of #variants with reduced #baloxavir marboxil #susceptibility after #treatment of #children with #influenza A during the 2018/2019 influenza season (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Detection of variants with reduced baloxavir marboxil susceptibility after treatment of children with influenza A during the 2018/2019 influenza season

Masatoki Sato, Emi Takashita, Masahiko Katayose, Kenji Nemoto, Nobuko Sakai, Koichi Hashimoto, Mitsuaki Hosoya

The Journal of Infectious Diseases, jiaa061, https://doi.org/10.1093/infdis/jiaa061

Published: 08 February 2020

 

Abstract

During the 2018–2019 influenza seasons, we detected reduced baloxavir marboxil (baloxavir) susceptible variants with I38S or I38T amino acid substitutions on the PA subunit of influenza virus RNA polymerase in 7 of 18 baloxavir treated children and found that virus titer rebounded in some of these children with variants. We also found fever durations to be similar between patients with or without the variants, but the patients with variants shed the virus 3 days longer and took longer to improve clinical symptoms than those without variants.

The emergence of these variants should be monitored during future influenza seasons.

influenza, baloxavir, oseltamivir, antiviral therapy, resistance

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This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Influenza A; Antivirals; Drugs Resistance; Baloxavir; Pediatrics.

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#Global #Update on the Susceptibilities of #Human #Influenza Viruses to #NAIs and the #Baloxavir, 2017-2018 (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res, 104718 2020 Jan 28 [Online ahead of print]

Global Update on the Susceptibilities of Human Influenza Viruses to Neuraminidase Inhibitors and the Cap-Dependent Endonuclease Inhibitor Baloxavir, 2017-2018

Emi Takashita 1, Rod S Daniels 2, Seiichiro Fujisaki 3, Vicki Gregory 2, Larisa V Gubareva 4, Weiijuan Huang 5, Aeron C Hurt 6, Angie Lackenby 7, Ha T Nguyen 4, Dmitriy Pereyaslov 8, Merryn Roe 6, Magdi Samaan 9, Kanta Subbarao 6, Herman Tse 10, Dayan Wang 5, Hui-Ling Yen 11, Wenqing Zhang 9, Adam Meijer 12

Affiliations: 1 WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan. Electronic address: emitaka@nih.go.jp. 2 WHO Collaborating Centre for Reference and Research on Influenza, The Francis Crick Institute, Worldwide Influenza Centre, 1 Midland Road, London, NW1 1AT, United Kingdom. 3 WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan. 4 WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, Centers for Diseases Control and Prevention, 1600 Clifton RD NE, MS-G16, Atlanta, GA, 30329, USA. 5 WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China. 6 WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. 7 National Infection Service, Public Health England, London, NW9 5HT, United Kingdom. 8 Division of Communicable Diseases, Health Security, & Environment, World Health Organization Regional Office for Europe, UN City, Marmorvej 51, DK-2100, Copenhagen Ø, Denmark. 9 Global Influenza Programme, World Health Organization, Avenue Appia 20, 1211, Geneva 27, Switzerland. 10 Public Health Laboratory Centre, 382 Nam Cheong Street, Hong Kong SAR, China. 11 School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. 12 National Institute for Public Health and the Environment, PO Box 1, 3720, BA Bilthoven, the Netherlands.

PMID: 32004620 DOI: 10.1016/j.antiviral.2020.104718

 

Abstract

The global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012-13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for the treatment of influenza virus infection in Japan and the United States. For this annual report, the susceptibilities of influenza viruses to NAIs and baloxavir were analyzed. A total of 15409 viruses, collected by World Health Organization (WHO) recognized National Influenza Centers and other laboratories between May 2017 and May 2018, were assessed for phenotypic NAI susceptibility by five WHO Collaborating Centers (CCs). The 50% inhibitory concentration (IC50) was determined for oseltamivir, zanamivir, peramivir and laninamivir. Reduced inhibition (RI) or highly reduced inhibition (HRI) by one or more NAIs was exhibited by 0.8% of viruses tested (n = 122). The frequency of viruses with RI or HRI has remained low since this global analysis began (2012-13: 0.6%; 2013-14: 1.9%; 2014-15: 0.5%; 2015-16: 0.8%; 2016-17: 0.2%). PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23 G/K/R, PA A36V, PA A37T, PA I38 F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions. Five of them were included in phenotypic baloxavir susceptibility analysis by two WHO CCs and IC50 values were determined. The PA variant viruses showed 6-17-fold reduced susceptibility to baloxavir. Overall, in the 2017-18 period the frequency of circulating influenza viruses with reduced susceptibility to NAIs or baloxavir was low, but continued monitoring is important.

Keywords: Baloxavir; Influenza; Neuraminidase inhibitor; Resistance; Surveillance; Susceptibility.

Copyright © 2020. Published by Elsevier B.V.

Conflict of interest statement: Declaration of competing interest None.

Keywords: Antivirals; Drugs Resistance; Influenza A; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Baloxavir.

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#Human #infection with a novel #reassortant #Eurasian-avian lineage #swine #H1N1 virus in northern #China (Emerg Microbes Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Emerg Microbes Infect. 2019;8(1):1535-1545. doi: 10.1080/22221751.2019.1679611.

Human infection with a novel reassortant Eurasian-avian lineage swine H1N1 virus in northern China.

Li X1, Guo L1, Liu C2, Cheng Y3, Kong M1, Yang L3, Zhuang Z1, Liu J3, Zou M1, Dong X1, Su X1, Gu Q1.

Author information: 1 Tianjin Centers for Disease Control and Prevention, Tianjin, People’s Republic of China. 2 Jizhou District Center for Disease Control and Prevention, Tianjin, People’s Republic of China. 3 Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China.

 

Abstract

Influenza A virus infections occur in different species, causing mild to severe respiratory symptoms that lead to a heavy disease burden. Eurasian avian-like swine influenza A(H1N1) viruses (EAS-H1N1) are predominant in pigs and occasionally infect humans. An influenza A(H1N1) virus was isolated from a boy who was suffering from fever and headache and designated as A/Tianjin-baodi/1606/2018(H1N1). Full-genome sequencing and phylogenetic analysis revealed that A/Tianjin-baodi/1606/2018(H1N1) is a novel reassortant EAS-H1N1 containing gene segments from EAS-H1N1 (HA and NA), classical swine H1N1(NS) and A(H1N1)pdm09(PB2, PB2, PA, NP and M) viruses. The isolation and analysis of A/Tianjin-baodi/1606/2018(H1) provide further evidence that EAS-H1N1 poses a threat to human health and greater attention should be paid to surveillance of influenza virus infection in pigs and humans.

KEYWORDS: EAS-H1N1; Influenza A virus; Phylogenetic analysis; molecular characteristics; triple-reassortant

PMID: 31661383 PMCID: PMC6830285 DOI: 10.1080/22221751.2019.1679611 [Indexed for MEDLINE] Free PMC Article

Keywords: Influenza A; Swine Influenza; H1N1; H1N1pdm09; Reassortant strain; Human; China.

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#Serological evidence of #swine exposure to #H1N1pdm09 #influenza A virus in #Burkina Faso (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2020 Feb;241:108572. doi: 10.1016/j.vetmic.2019.108572. Epub 2019 Dec 31.

Serological evidence of swine exposure to pandemic H1N1/2009 influenza A virus in Burkina Faso.

Tialla D1, Sausy A2, Cissé A3, Sagna T4, Ilboudo AK5, Ouédraogo GA6, Hübschen JM7, Tarnagda Z8, Snoeck CJ9.

Author information: 1 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso; Ecole Nationale de l’Elevage et de la Santé Animale (ENESA), Secteur 28, Ouagadougou, Burkina Faso. Electronic address: tialladfaso@yahoo.fr. 2 Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address: aurelie.sausy@lih.lu. 3 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: assanacisse@yahoo.fr. 4 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: stanilinda@gmail.com. 5 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: ilboudokader@yahoo.fr. 6 Laboratoire de Recherche et d’Enseignement en Santé et Biotechnologies Animales (LARESBA), Université Nazi Boni, 01 BP 109, Bobo-Dioulasso, Burkina Faso. Electronic address: ogeorgesanicet@yahoo.fr. 7 Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address: judith.huebschen@lih.lu. 8 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: zekiba@hotmail.com. 9 Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address: chantal.snoeck@lih.lu.

 

Abstract

Despite improvement of human and avian influenza surveillance, swine influenza surveillance in sub-Saharan Africa is scarce and pandemic preparedness is still deemed inadequate, including in Burkina Faso. This cross-sectional study therefore aimed to investigate the (past) exposure of pigs to influenza A viruses. Practices of people with occupational contacts with pigs and their knowledge on influenza A were investigated in order to formulate future prevention guidelines. In 2016-2017, pig nasopharyngeal swabs and sera were collected and screened for the presence of influenza virus by RT-PCR or of anti-influenza antibodies by competitive ELISA. Seropositive samples were further characterized in virus microneutralization assays against human and swine H1N1 virus strains. Nasopharyngeal swabs were obtained from people with occupational contact with pigs and screened similarly. Demographic data as well as practices related to their profession were recorded. No influenza A virus was detected in nasopharyngeal swabs in humans (n = 358) or in pigs (n = 600). Seroprevalence in pigs reached 6.8 % (41/600) and seropositive animals were found in 50.0 % of extensive settings (10/20) and 19.0 % of (semi-)intensive farms (4/21). All positive sera reacted against the pandemic H1N1/2009 strain, while seropositivity against two Eurasian avian-like and one American swine H1N1 strains and individual titers were lower. These results suggested exposure to pandemic H1N1/2009 virus and cross-reactivity to other H1N1 strains. Farmers with higher frequency of contact to pigs, absence of protective equipment and lack of knowledge on zoonoses are likely key players in driving human-to-swine virus transmission.

Copyright © 2020 Elsevier B.V. All rights reserved.

KEYWORDS: Burkina Faso; Epidemiology; Influenza A virus; Pandemic H1N1/2009; Pigs; Public health; Reverse zoonosis

PMID: 31928706 DOI: 10.1016/j.vetmic.2019.108572

Keywords: Influenza A; H1N1pdm09; Pigs; Burkina Faso.

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