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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.

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

PLoS ONE, Vol 16, Iss 5, p e

2021 Volume 0251473

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.
Keywords	Medicine ; R ; Science ; Q
Subject code	570 ; 572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Month of Influenza Virus Vaccination Influences Antibody Responses in Children and Adults

Rhiannon R. Penkert / Nehali Patel / Richard J. Webby / Ted M. Ross / Julia L. Hurwitz

Vaccines, Vol 9, Iss 2, p

2021 Volume 68

Abstract: The improvement of influenza virus vaccines and the development of a universal product have been long-standing goals in pre-clinical and clinical research. To meet these goals and to understand the strengths and weaknesses of current vaccine strategies, ... ...

Abstract	The improvement of influenza virus vaccines and the development of a universal product have been long-standing goals in pre-clinical and clinical research. To meet these goals and to understand the strengths and weaknesses of current vaccine strategies, scientists routinely study human responses toward seasonal influenza vaccines. This research is frequently performed with clinical samples taken throughout an influenza season, often without strict attention to the month of inoculation for each study participant. Here, we ask how the timing of vaccination affects outcomes. Results demonstrate significant influences of inoculation month on the immune response. During the progression from fall to winter months, there are changes in host lifestyles and in the frequencies of clinical/sub-clinical viral infections that can significantly alter vaccine immunogenicity. We now recommend routine assessment of inoculation month during clinical studies to inform data interpretation and expedite the development of successful vaccines. This recommendation is pertinent to numerous vaccine development efforts within and outside the influenza virus field.
Keywords	month ; influenza virus ; immune response ; vaccination ; hemagglutination inhibition ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: H5 influenza, a global update

Harfoot, Rhodri / Richard J. Webby

journal of microbiology. 2017 Mar., v. 55, no. 3

2017

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.
Keywords	Influenza A virus ; evolution ; geese ; humans ; influenza ; mortality ; pathogenicity ; viruses
Language	English
Dates of publication	2017-03
Size	p. 196-203.
Publishing place	The Microbiological Society of Korea
Document type	Article
Note	Review
ZDB-ID	2012399-1
ISSN	1225-8873
ISSN	1225-8873
DOI	10.1007/s12275-017-7062-7
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus

Brianna L. Bullard / Brigette N. Corder / Jennifer DeBeauchamp / Adam Rubrum / Bette Korber / Richard J. Webby / Eric A. Weaver

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 14

Abstract: A range of Influenza vaccines have been linked to induction of adaptive immunity in a number of animal models. Here, the authors utilize a computational design strategy and produce a swine H3 influenza vaccine which shows enhanced efficacy in both murine ...

Abstract	A range of Influenza vaccines have been linked to induction of adaptive immunity in a number of animal models. Here, the authors utilize a computational design strategy and produce a swine H3 influenza vaccine which shows enhanced efficacy in both murine and porcine infectious disease models.
Keywords	Science ; Q
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Birth cohort relative to an influenza A virus's antigenic cluster introduction drives patterns of children's antibody titers.

Andrew F Brouwer / Angel Balmaseda / Lionel Gresh / Mayuri Patel / Sergio Ojeda / Amy J Schiller / Roger Lopez / Richard J Webby / Martha I Nelson / Guillermina Kuan / Aubree Gordon

PLoS Pathogens, Vol 18, Iss 2, p e

2022 Volume 1010317

Abstract: An individual's antibody titers to influenza A strains are a result of the complicated interplay between infection history, cross-reactivity, immune waning, and other factors. It has been challenging to disentangle how population-level patterns of ... ...

Abstract	An individual's antibody titers to influenza A strains are a result of the complicated interplay between infection history, cross-reactivity, immune waning, and other factors. It has been challenging to disentangle how population-level patterns of humoral immunity change as a function of age, calendar year, and birth cohort from cross-sectional data alone. We analyzed 1,589 longitudinal sera samples from 260 children across three studies in Nicaragua, 2006-16. Hemagglutination inhibition (HAI) titers were determined against four H3N2 strains, one H1N1 strain, and two H1N1pdm strains. We assessed temporal patterns of HAI titers using an age-period-cohort modeling framework. We found that titers against a given virus depended on calendar year of serum collection and birth cohort but not on age. Titer cohort patterns were better described by participants' ages relative to year of likely introduction of the virus's antigenic cluster than by age relative to year of strain introduction or by year of birth. These cohort effects may be driven by a decreasing likelihood of early-life infection after cluster introduction and by more broadly reactive antibodies at a young age. H3N2 and H1N1 viruses had qualitatively distinct cohort patterns, with cohort patterns of titers to specific H3N2 strains reaching their peak in children born 3 years prior to that virus's antigenic cluster introduction and with titers to H1N1 and H1N1pdm strains peaking for children born 1-2 years prior to cluster introduction but not being dramatically lower for older children. Ultimately, specific patterns of strain circulation and antigenic cluster introduction may drive population-level antibody titer patterns in children.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reduced airborne transmission of SARS-CoV-2 BA.1 Omicron virus in Syrian hamsters

Adrianus C. M. Boon / Tamarand L. Darling / Peter J. Halfmann / John Franks / Richard J. Webby / Dan H. Barouch / Julia R. Port / Vincent J. Munster / Michael S. Diamond / Yoshihiro Kawaoka

PLoS Pathogens, Vol 18, Iss

2022 Volume 12

Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Centralized Consensus Hemagglutinin Genes Induce Protective Immunity against H1, H3 and H5 Influenza Viruses.

Richard J Webby / Eric A Weaver

PLoS ONE, Vol 10, Iss 10, p e

2015 Volume 0140702

Abstract: With the exception of the live attenuated influenza vaccine there have been no substantial changes in influenza vaccine strategies since the 1940's. Here we report an alternative vaccine approach that uses Adenovirus-vectored centralized hemagglutinin ( ... ...

Abstract	With the exception of the live attenuated influenza vaccine there have been no substantial changes in influenza vaccine strategies since the 1940's. Here we report an alternative vaccine approach that uses Adenovirus-vectored centralized hemagglutinin (HA) genes as vaccine antigens. Consensus H1-Con, H3-Con and H5-Con HA genes were computationally derived. Mice were immunized with Ad vaccines expressing the centralized genes individually. Groups of mice were vaccinated with 1 X 1010, 5 X 107 and 1 X 107 virus particles per mouse to represent high, intermediate and low doses, respectively. 100% of the mice that were vaccinated with the high dose vaccine were protected from heterologous lethal challenges within each subtype. In addition to 100% survival, there were no signs of weight loss and disease in 7 out of 8 groups of high dose vaccinated mice. Lower doses of vaccine showed a reduction of protection in a dose-dependent manner. However, even the lowest dose of vaccine provided significant levels of protection against the divergent influenza strains, especially considering the stringency of the challenge virus. In addition, we found that all doses of H5-Con vaccine were capable of providing complete protection against mortality when challenged with lethal doses of all 3 H5N1 influenza strains. This data demonstrates that centralized H1-Con, H3-Con and H5-Con genes can be effectively used to completely protect mice against many diverse strains of influenza. Therefore, we believe that these Ad-vectored centralized genes could be easily translated into new human vaccines.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic and Antigenic Characteristics of Highly Pathogenic Avian Influenza A(H5N8) Viruses Circulating in Domestic Poultry in Egypt, 2017–2021

Ahmed Kandeil / Yassmin Moatasim / Ahmed El Taweel / Mohamed El Sayes / Adam Rubrum / Trushar Jeevan / Pamela P. McKenzie / Richard J. Webby / Mohamed A. Ali / Ghazi Kayali / Rabeh El-Shesheny

Microorganisms, Vol 10, Iss 595, p

2022 Volume 595

Abstract: In Egypt, the endemicity of avian influenza viruses is a serious concern. Since 2016, several outbreaks of H5N8 have been recorded among domestic poultry in various areas of the country. Active surveillance of domestic poultry across several governorates ...

Abstract	In Egypt, the endemicity of avian influenza viruses is a serious concern. Since 2016, several outbreaks of H5N8 have been recorded among domestic poultry in various areas of the country. Active surveillance of domestic poultry across several governorates in Egypt from 2017 to 2021 detected at least six genotypes of Highly Pathogenic Avian Influenza (HPAI) H5N8 viruses with evidence of partial or complete annual replacement of dominant strains. Although all Egyptian H5N8 viruses had clade 2.3.4.4b hemagglutinin (HA) genes, the remaining viral gene segments were from multiple geographic origins, indicating that the H5N8 isolates resulted from multiple introductions. Mutations in the viral proteins associated with pathogenicity and antiviral drug resistance were detected. Some mutations in the HA resulted in antigenic drift. Heterogeneity in circulating H5N8 HPAI threatens poultry production and public health.
Keywords	Egypt ; highly pathogenic avian influenza ; H5N8 ; phylogenetic analysis ; reassortment ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Incidence and neutralizing antibody seroprevalence of influenza B virus in Egypt

Noura M Abo Shama / Sara H Mahmoud / Ola Bagato / Elsayed Tarek AbdElsalam / Maha Alkhazindar / Ahmed Kandeil / Pamela P McKenzie / Richard J Webby / Mohamed A Ali / Ghazi Kayali / Rabeh El-Shesheny

PLoS ONE, Vol 17, Iss 6, p e

Results of a community-based cohort study.

2022 Volume 0269321

Abstract: Since 2000, two lineages of influenza B viruses, Victoria and Yamagata, have been circulating at similar frequencies worldwide. Little is known about the circulation of those viruses in Egypt. This study aims to describe the epidemiology of influenza B ... ...

Abstract	Since 2000, two lineages of influenza B viruses, Victoria and Yamagata, have been circulating at similar frequencies worldwide. Little is known about the circulation of those viruses in Egypt. This study aims to describe the epidemiology of influenza B virus infections in Egypt, 2017-2019. This was performed through a household prospective cohort study on influenza infections among 2400 individuals from five villages. When a study participant had influenza like symptoms, a nasal swab and an oropharyngeal swab were obtained and tested by RT-PCR for influenza B infections. A serum sample was obtained from all participants annually to detect neutralizing antibodies using microneutralization assay. 9.1% of subjects were positive for influenza B viruses during season 2017-2018 mostly among preschoolers and 7.6% were positive during the season 2018-2019 with higher risk in females, potentially due to mothers being infected after contact with their children. The overall seroprevalence among the participants was 53.2% and 52.2% against the Victoria and Yamagata lineages respectively, the majority of seropositive participants were students. Multivariate analysis showed that age and having chronic diseases were the strongest predictors of infection. Our results show that both influenza B lineages circulated between 2017 and 2020 in Egypt almost in equal proportion. Encouraging the uptake of seasonal influenza vaccines is recommended.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Host diversity and behavior determine patterns of interspecies transmission and geographic diffusion of avian influenza A subtypes among North American wild reservoir species.

Joseph T Hicks / Kimberly Edwards / Xueting Qiu / Do-Kyun Kim / James E Hixson / Scott Krauss / Richard J Webby / Robert G Webster / Justin Bahl

PLoS Pathogens, Vol 18, Iss 4, p e

2022 Volume 1009973

Abstract: Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic ... ...

Abstract	Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic sequences from North American wild birds, including 303 newly sequenced isolates, to estimate interspecies and geographic viral transition patterns among multiple co-circulating subtypes. Our results show high transition rates within Anseriformes and Charadriiformes, but limited transitions between these orders. Patterns of transition between species were positively associated with breeding habitat range overlap, and negatively associated with host genetic distance. Distance between regions (negative correlation) and summer temperature at origin (positive correlation) were strong predictors of transition between locations. Taken together, this study demonstrates that host diversity and ecology can determine evolutionary processes that underlie AIV natural history and spread. Understanding these processes can provide important insights for effective control of AIV.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	590
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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