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Article ; Online: An algorithm for the characterization of influenza A viruses from various host species and environments.

Pulscher, Laura A / Webby, Richard J / Gray, Gregory C

2024 Volume 18, Issue 2, Page(s) e13258

Abstract: Due to the extensive host range of influenza A viruses, it is difficult to determine the best diagnostic algorithm to efficiently screen samples from a variety of host species for influenza A viruses. While there are some influenza diagnostic algorithms ... ...

Abstract	Due to the extensive host range of influenza A viruses, it is difficult to determine the best diagnostic algorithm to efficiently screen samples from a variety of host species for influenza A viruses. While there are some influenza diagnostic algorithms that are specific to host species, to our knowledge, no single algorithm exists for the characterization of influenza A viruses across multiple host species. In this paper, we propose an algorithm that can serve as a guide for screening human, animal, and environmental samples for influenza A viruses of high human and animal health importance.
MeSH term(s)	Animals ; Humans ; Influenza A virus/genetics ; Algorithms ; Host Specificity ; Influenza, Human/diagnosis
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2274538-5
ISSN	1750-2659 ; 1750-2640
ISSN (online)	1750-2659
ISSN	1750-2640
DOI	10.1111/irv.13258
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Zs.A 6568: Show issues

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Article ; Online: Editorial Commentary: This Little Piggy Went to Market-but Perhaps Should Have Stayed Home.

Webby, Richard J

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2015 Volume 61, Issue 9, Page(s) 1363–1364

MeSH term(s)	Animals ; Humans ; Influenza A virus/isolation & purification ; Marketing ; Occupational Exposure ; Orthomyxoviridae Infections/veterinary ; Swine Diseases/transmission ; Zoonoses/transmission
Language	English
Publishing date	2015-11-01
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/civ620
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Article ; Online: The evolution and future of influenza pandemic preparedness.

Harrington, Walter N / Kackos, Christina M / Webby, Richard J

Experimental & molecular medicine

2021 Volume 53, Issue 5, Page(s) 737–749

Abstract: The influenza virus is a global threat to human health causing unpredictable yet recurring pandemics, the last four emerging over the course of a hundred years. As our knowledge of influenza virus evolution, distribution, and transmission has increased, ... ...

Abstract	The influenza virus is a global threat to human health causing unpredictable yet recurring pandemics, the last four emerging over the course of a hundred years. As our knowledge of influenza virus evolution, distribution, and transmission has increased, paths to pandemic preparedness have become apparent. In the 1950s, the World Health Organization (WHO) established a global influenza surveillance network that is now composed of institutions in 122 member states. This and other surveillance networks monitor circulating influenza strains in humans and animal reservoirs and are primed to detect influenza strains with pandemic potential. Both the United States Centers for Disease Control and Prevention and the WHO have also developed pandemic risk assessment tools that evaluate specific aspects of emerging influenza strains to develop a systematic process of determining research and funding priorities according to the risk of emergence and potential impact. Here, we review the history of influenza pandemic preparedness and the current state of preparedness, and we propose additional measures for improvement. We also comment on the intersection between the influenza pandemic preparedness network and the current SARS-CoV-2 crisis. We must continually evaluate and revise our risk assessment and pandemic preparedness plans and incorporate new information gathered from research and global crises.
MeSH term(s)	Animals ; COVID-19/epidemiology ; COVID-19/prevention & control ; Humans ; Influenza A virus/isolation & purification ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Pandemics/prevention & control ; Risk Assessment ; World Health Organization
Language	English
Publishing date	2021-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-021-00603-0
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Zs.A 4775: Show issues

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Article ; Online: Interplay between H1N1 influenza a virus infection, extracellular and intracellular respiratory tract pH, and host responses in a mouse model.

Okda, Faten A / Perry, S Scott / Webby, Richard J / Russell, Charles J

PloS one

2021 Volume 16, Issue 5, Page(s) e0251473

Abstract: During influenza A virus (IAV) entry, the hemagglutinin (HA) protein is triggered by endosomal low pH to undergo irreversible structural changes that mediate membrane fusion. HA proteins from different isolates vary in the pH at which they become ... ...

Abstract	During influenza A virus (IAV) entry, the hemagglutinin (HA) protein is triggered by endosomal low pH to undergo irreversible structural changes that mediate membrane fusion. HA proteins from different isolates vary in the pH at which they become activated in endosomes or become irreversible inactivated if exposed to extracellular acid. Little is known about extracellular pH in the upper respiratory tracts of mammals, how pH may shift during IAV infection, and its impact on replication of viruses that vary in HA activation pH. Here, we inoculated DBA/2J mice intranasally with A/TN/1-560/2009 (H1N1) (activation pH 5.5) or a mutant containing the destabilizing mutation HA1-Y17H (pH 6.0). We measured the kinetics of extracellular pH during infection using an optical pH-sensitive microsensor probe placed in the naris, nasal sinus, soft palate, and trachea. We also measured intracellular pH of single-cell suspensions of live, primary lung epithelial cells with various wavelength pH-sensitive dyes localized to cell membranes, cytosol, endosomes, secretory vesicles, microtubules, and lysosomes. Infection with either virus decreased extracellular pH and increased intracellular pH. Peak host immune responses were observed at 2 days post infection (DPI) and peak pH changes at 5 DPI. Extracellular and intracellular pH returned to baseline by 7 DPI in mice infected with HA1-Y17H and was restored later in wildtype-infected. Overall, IAV infection altered respiratory tract pH, which in turn modulated replication efficiency. This suggests a virus-host pH feedback loop that may select for IAV strains containing HA proteins of optimal pH stability, which may be approximately pH 5.5 in mice but may differ in other species.
MeSH term(s)	Animals ; Disease Models, Animal ; Hydrogen-Ion Concentration ; Immunity/physiology ; Influenza A Virus, H1N1 Subtype ; Mice ; Orthomyxoviridae Infections/physiopathology ; Respiratory System/physiopathology ; Respiratory System/virology ; Virus Internalization ; Virus Replication
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0251473
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Article ; Online: Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice.

Pekarek, Matthew J / Petro-Turnquist, Erika M / Rubrum, Adam / Webby, Richard J / Weaver, Eric A

Viruses

2022 Volume 14, Issue 6

Abstract: Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouse-adapting IBV can produce highly pathogenic viruses through ... ...

Abstract	Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouse-adapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin-Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research.
MeSH term(s)	Amino Acid Sequence ; Animals ; Dogs ; Eggs ; Influenza B virus/genetics ; Influenza Vaccines ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections
Chemical Substances	Influenza Vaccines
Language	English
Publishing date	2022-06-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061299
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Article ; Online: Effect of E23G/K, F36V, N37T, E119D, and E199G polymerase acidic protein substitutions on the replication and baloxavir susceptibility of influenza B viruses.

Pascua, Philippe Noriel Q / Jones, Jeremy C / Webby, Richard J / Govorkova, Elena A

Antiviral research

2022 Volume 208, Page(s) 105455

Abstract: Baloxavir marboxil (baloxavir) is a highly effective, single-dose influenza therapeutic. Identification of molecular markers in the target polymerase acidic (PA) protein that can diminish baloxavir efficacy is an ongoing goal of the scientific community. ...

Abstract	Baloxavir marboxil (baloxavir) is a highly effective, single-dose influenza therapeutic. Identification of molecular markers in the target polymerase acidic (PA) protein that can diminish baloxavir efficacy is an ongoing goal of the scientific community. In this study, we generated recombinant Victoria-lineage and Yamagata-lineage influenza B viruses (IBVs) containing 6 substitutions (E23G/K, F36V, N37T, E119D, and E199G) spanning the endonuclease domain of the PA. Although 5 of these PA substitutions negatively impacted in vitro polymerase activity and replication kinetics, particularly in the Victoria-lineage IBV background, viruses with E119D exhibited activity levels comparable to those of wild-type viruses. Moreover, only E119D moderately decreased the susceptibility of IBVs to baloxavir (resulting in ∼2.0-fold to 2.6-fold elevated EC
MeSH term(s)	Influenza B virus/genetics ; Drug Resistance, Viral/genetics ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Dibenzothiepins/pharmacology
Chemical Substances	baloxavir (4G86Y4JT3F) ; Antiviral Agents ; Dibenzothiepins
Language	English
Publishing date	2022-10-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2022.105455
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Zs.A 1627: Show issues

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Article ; Online: Influenza A virus polymerase acidic protein E23R substitution is a marker of reduced susceptibility to baloxavir.

Jones, Jeremy C / Rovito, Samuel W / Penaflor, Melissa K / Webby, Richard J / Govorkova, Elena A

Antiviral research

2022 Volume 204, Page(s) 105369

Abstract: In our ongoing efforts to identify baloxavir resistance markers, we demonstrated that the influenza A polymerase acidic (PA) protein E23R substitution is genetically stable, increases baloxavir ... ...

Abstract	In our ongoing efforts to identify baloxavir resistance markers, we demonstrated that the influenza A polymerase acidic (PA) protein E23R substitution is genetically stable, increases baloxavir EC
MeSH term(s)	Amino Acid Substitution ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Dibenzothiepins ; Drug Resistance, Viral/genetics ; Humans ; Influenza A virus/genetics ; Influenza, Human/drug therapy ; Morpholines ; Oxazines/pharmacology ; Oxazines/therapeutic use ; Pyridines/pharmacology ; Pyridones/pharmacology ; Pyridones/therapeutic use ; Thiepins/pharmacology ; Thiepins/therapeutic use ; Triazines/pharmacology ; Triazines/therapeutic use
Chemical Substances	Antiviral Agents ; Dibenzothiepins ; Morpholines ; Oxazines ; Pyridines ; Pyridones ; Thiepins ; Triazines ; baloxavir (4G86Y4JT3F)
Language	English
Publishing date	2022-06-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2022.105369
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Article ; Online: The changing landscape of A H7N9 influenza virus infections in China.

Webby, Richard J / Yang, Zifeng

The Lancet. Infectious diseases

2017 Volume 17, Issue 8, Page(s) 783–784

MeSH term(s)	Animals ; China ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza in Birds ; Influenza, Human ; Poultry
Language	English
Publishing date	2017-06-02
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(17)30337-7
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Article ; Online: Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice.

Nichols, Jacob H / Williams, Evan P / Parvathareddy, Jyothi / Cao, Xueyuan / Kong, Ying / Fitzpatrick, Elizabeth / Webby, Richard J / Jonsson, Colleen B

Viruses

2023 Volume 15, Issue 4

Abstract: The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection ... ...

Abstract	The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection conferred by earlier strains following infection or vaccination to each new VOC. We hypothesized that while NAbs play a major role in protection against infection and disease, a heterologous reinfection or challenge may gain a foothold in the upper respiratory tract (URT) and result in a self-limited viral infection accompanied by an inflammatory response. To test this hypothesis, we infected K18-hACE2 mice with SARS-CoV-2 USA-WA1/2020 (WA1) and, after 24 days, challenged with WA1, Alpha, or Delta. While NAb titers against each virus were similar across all cohorts prior to challenge, the mice challenged with Alpha and Delta showed weight loss and upregulation of proinflammatory cytokines in the URT and lower RT (LRT). Mice challenged with WA1 showed complete protection. We noted increased levels of viral RNA transcripts only in the URT of mice challenged with Alpha and Delta. In conclusion, our results suggested self-limiting breakthrough infections of Alpha or Delta in the URT, which correlated with clinical signs and a significant inflammatory response in mice.
MeSH term(s)	Animals ; Humans ; Mice ; SARS-CoV-2/genetics ; COVID-19 ; Respiratory Tract Infections
Chemical Substances	K-18 conjugate
Language	English
Publishing date	2023-04-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15040946
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Article ; Online: H5 influenza, a global update.

Harfoot, Rhodri / Webby, Richard J

Journal of microbiology (Seoul, Korea)

2017 Volume 55, Issue 3, Page(s) 196–203

Abstract: H5 influenza viruses have caused much alarm globally due to their high pathogenic potential. As yet we have not seen sustained spread of the virus amongst humans despite a high prevalence of the virus in avian populations. Nevertheless, isolated human ... ...

Abstract	H5 influenza viruses have caused much alarm globally due to their high pathogenic potential. As yet we have not seen sustained spread of the virus amongst humans despite a high prevalence of the virus in avian populations. Nevertheless, isolated human cases of infection have demonstrated high mortality and there are substantial efforts being taken to monitor the evolution of the virus and to undertake preparedness activities. Here we review and discuss the evolution of the A/goose/Guangdong/1/96 (H5N1) virus with emphasis on recent events.
MeSH term(s)	Animals ; Chickens ; Disease Outbreaks ; Evolution, Molecular ; Geese/virology ; Genetic Variation ; Global Health ; Hemagglutinin Glycoproteins, Influenza Virus ; Humans ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza A Virus, H5N1 Subtype/pathogenicity ; Influenza Vaccines ; Influenza in Birds/epidemiology ; Influenza in Birds/transmission ; Influenza in Birds/virology ; Influenza, Human/epidemiology ; Influenza, Human/transmission ; Influenza, Human/virology ; Phylogeny
Chemical Substances	Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines
Language	English
Publishing date	2017-03
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2012399-1
ISSN	1976-3794 ; 1225-8873
ISSN (online)	1976-3794
ISSN	1225-8873
DOI	10.1007/s12275-017-7062-7
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