#Virulence of three #European highly pathogenic #H7N1 and #H7N7 #avian #influenza viruses in Pekin and Muscovy #ducks (BMC Vet Res., abstract)

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

BMC Vet Res. 2019 May 10;15(1):142. doi: 10.1186/s12917-019-1899-4.

Virulence of three European highly pathogenic H7N1 and H7N7 avian influenza viruses in Pekin and Muscovy ducks.

Scheibner D1, Blaurock C1, Mettenleiter TC1, Abdelwhab EM2.

Author information: 1 Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany. 2 Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany. sayed.abdel-whab@fli.de.

 

Abstract

BACKGROUND:

There is paucity of data on the virulence of highly pathogenic (HP) avian influenza viruses (AIV) H7 in ducks compared to HPAIV H5. Here, the virulence of HPAIV H7N1 (designated H7N1-FPV34 and H7N1-It99) and H7N7 (designated H7N7-FPV27) was assessed in Pekin and/or Muscovy ducklings after intrachoanal (IC) or intramuscular (IM) infection.

RESULTS:

The morbidity rate ranged from 60 to 100% and mortality rate from 20 to 80% depending on the duck species, virus strain and/or challenge route. All Muscovy ducklings inoculated IC with H7N7-FPV27 or H7N1-FPV34 exhibited mild to severe clinical signs resulting in the death of 2/10 and 8/10 ducklings, respectively. Also, 2/10 and 6/9 of inoculated Muscovy ducklings died after IC or IM infection with H7N1-It99, respectively. Moreover, 5/10 Pekin ducklings inoculated IC or IM with H7N1-It99 died. The level of virus detected in the oropharyngeal swabs was higher than in the cloacal swabs.

CONCLUSION:

Taken together, HPAIV H7 cause mortality and morbidity in Muscovy and Pekin ducklings. The severity of disease in Muscovy ducklings depended on the virus strain and/or route of infection. Preferential replication of the virus in the respiratory tract compared to the gut merits further investigation.

KEYWORDS: Ducks; H7N1; H7N7; HPAIV; Highly pathogenic avian influenza virus; Muscovy duck; Pekin duck; Virulence

PMID: 31077209 PMCID: PMC6511205 DOI: 10.1186/s12917-019-1899-4 [Indexed for MEDLINE] Free PMC Article

Keywords: Avian Influenza; H7N1; H7N7; Poultry; Animal models.

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Bactrian #camels shed large quantities of Middle East respiratory syndrome #coronavirus (#MERS-CoV) after experimental #infection (Emerg Microbes Infect., abstract)

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

Emerg Microbes Infect. 2019;8(1):717-723. doi: 10.1080/22221751.2019.1618687.

Bactrian camels shed large quantities of Middle East respiratory syndrome coronavirus (MERS-CoV) after experimental infection.

Adney DR1, Letko M2, Ragan IK1, Scott D2, van Doremalen N2, Bowen RA1, Munster VJ2.

Author information: 1 a Department of Biomedical Sciences , Colorado State University , Fort Collins , CO , USA. 2 b Rocky Mountain Laboratories , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton , MT , USA.

 

Abstract

In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged. To date, more than 2300 cases have been reported, with an approximate case fatality rate of 35%. Epidemiological investigations identified dromedary camels as the source of MERS-CoV zoonotic transmission and evidence of MERS-CoV circulation has been observed throughout the original range of distribution. Other new-world camelids, alpacas and llamas, are also susceptible to MERS-CoV infection. Currently, it is unknown whether Bactrian camels are susceptible to infection. The distribution of Bactrian camels overlaps partly with that of the dromedary camel in west and central Asia. The receptor for MERS-CoV, DPP4, of the Bactrian camel was 98.3% identical to the dromedary camel DPP4, and 100% identical for the 14 residues which interact with the MERS-CoV spike receptor. Upon intranasal inoculation with 107 plaque-forming units of MERS-CoV, animals developed a transient, primarily upper respiratory tract infection. Clinical signs of the MERS-CoV infection were benign, but shedding of large quantities of MERS-CoV from the URT was observed. These data are similar to infections reported with dromedary camel infections and indicate that Bactrians are susceptible to MERS-CoV and given their overlapping range are at risk of introduction and establishment of MERS-CoV within the Bactrian camel populations.

KEYWORDS: Bactrian camel; MERS-CoV; dromedary camel; natural reservoir; virus shedding

PMID: 31119984 DOI: 10.1080/22221751.2019.1618687

Keywords: MERS-CoV; Camels: Animal models.

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Shift from primary #pneumonic to secondary #septicemic #plague by decreasing the volume of intranasal challenge with #Yersinia pestis in the murine model (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model

Rachel M. Olson , Deborah M. Anderson

Published: May 23, 2019 / DOI: https://doi.org/10.1371/journal.pone.0217440

 

Abstract

Yersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered. In this work, we show that primary pneumonic or secondary septicemic plague can be preferentially modeled in mice by varying the volume used for intranasal delivery of Y. pestis. Low volume intranasal challenge (10μL) of wild type Y. pestis resulted in a high frequency of lethal secondary septicemic plague, with a low degree of primary lung infection and rapid development of sepsis. In contrast, high volume intranasal challenge (30μL) yielded uniform early lung infection and primary disease and a significant increase in lethality. In a commonly used BSL2 model, high volume challenge with Y. pestis lacking the pigmentation locus (pgm-) gave 105-fold greater deposition compared to low volume challenge, yet moribund mice did not develop severe lung disease and there was no detectable difference in lethality. These data indicate the primary cause of death of mice in the BSL2 model is sepsis regardless of intranasal dosing method. Overall, these findings allow for the preferential modeling of pneumonic or septicemic plague by intranasal dosing of mice with Y. pestis.

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Citation: Olson RM, Anderson DM (2019) Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestisin the murine model. PLoS ONE 14(5): e0217440. https://doi.org/10.1371/journal.pone.0217440

Editor: Matthew B. Lawrenz, University of Louisville School of Medicine, UNITED STATES

Received: February 24, 2019; Accepted: May 10, 2019; Published: May 23, 2019

Copyright: © 2019 Olson, Anderson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: Financial support for this work came from the National Institutes of Health/ National Institute of Allergy and Infectious Disease, public health service award #R01A129996 (DA). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Yersinia pestis; Pneumonic plague; Septicemic plague; Sepsis; Animal models.

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#PB2 and #hemagglutinin #mutations confer a #virulent phenotype on an #H1N2 #avian #influenza virus in mice (Arch Virol., abstract)

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

Arch Virol. 2019 May 20. doi: 10.1007/s00705-019-04283-0. [Epub ahead of print]

PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice.

Yu Z1, Ren Z2, Zhao Y3, Cheng K4, Sun W3, Zhang X3, Wu J5, He H6, Xia X7, Gao Y8.

Author information: 1 Institute of Poultry Science, Shandong Academy of Agricultural Sciences, No. 1 Jiaoxiao road, Jinan, 250023, Shandong, China. zhijun0215@gmail.com. 2 Joint National Laboratory for Antibody Drug Engineering, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China. 3 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China. 4 Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China. 5 Institute of Poultry Science, Shandong Academy of Agricultural Sciences, No. 1 Jiaoxiao road, Jinan, 250023, Shandong, China. 6 College of Life Sciences, Shandong Normal University, Jinan, 250014, China. 7 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China. xiaxzh@cae.cn. 8 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China. gaoyuwei@gmail.com.

 

Abstract

We previously obtained mouse-adapted variants of H1N2 avian influenza virus that contained PB2-L134H, PB2-I647L, PB2-D701N, HA-G228S, and M1-D231N mutations. Here, we analyzed the effects of these mutations on viral pathogenicity in a mammalian model. By evaluating the virulence of mouse-adapted H1N2 variants at different generations, we found that the PB2-D701N and HA-G228S mutations both contribute to the virulence of this virus in mammals. Furthermore, we found that the PB2-D701N and HA-G228S mutations both enhance the ability of the virus to replicate in vivo and in vitro and that the PB2-D701N substitution results in an expansion of viral tissue tropism. These results suggest that the PB2-D701N mutation and the HA-G228S mutation are the major mammalian determinants of H1N2 virus. These results help us to understand more about the mechanisms by which influenza viruses adapt to mammals, and monitoring of these mutations can be used in continuous influenza surveillance to assess the pandemic potential of avian influenza virus variants.

PMID: 31111259 DOI: 10.1007/s00705-019-04283-0

Keywords: Avian Influenza; H1N2; Reassortant strain; Animal models.

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#Mucosal #Immunity against #Neuraminidase Prevents #Influenza B Virus #Transmission in Guinea Pigs (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

Meagan McMahon, Ericka Kirkpatrick, Daniel Stadlbauer, Shirin Strohmeier, Nicole M. Bouvier, Florian Krammer

Stacey Schultz-Cherry, Editor

DOI: 10.1128/mBio.00560-19

 

ABSTRACT

Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses.

 

IMPORTANCE

Recently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.

Keywords: Seasonal Influenza; Influenza B; Vaccines; Animal models.

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Sequential #Immunization With Live-Attenuated Chimeric #Hemagglutinin-Based Vaccines Confers #Heterosubtypic Immunity Against #Influenza A Viruses in a Preclinical Ferret Model (Front Immunol., abstract)

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

Front Immunol. 2019 Apr 10;10:756. doi: 10.3389/fimmu.2019.00756. eCollection 2019.

Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model.

Liu WC1,2, Nachbagauer R1, Stadlbauer D1, Solórzano A1, Berlanda-Scorza F3, García-Sastre A1,2,4, Palese P1,4, Krammer F1, Albrecht RA1,2.

Author information: 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 2 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 3 PATH US, Seattle, WA, United States. 4 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

 

Abstract

Due to continuous antigenic drift and occasional antigenic shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with “exotic” head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4+IFN-γ+ and CD8+IFN-γ+ effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here.

KEYWORDS: chimeric hemagglutinin; ferret; heterosubtypic protection; live-attenuated influenza vaccine; stalk antibody; universal influenza virus vaccine

PMID: 31105689 PMCID: PMC6499175 DOI: 10.3389/fimmu.2019.00756

Keywords: Influenza A; Vaccines; Animal models.

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#Bacterial Factors Required for #Transmission of #Streptococcus pneumoniae in #Mammalian Hosts (Cell Host Microbe, abstract)

[Source: Cell, Host & Microbe, full page: (LINK). Abstract, edited.]

Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts

Hannah M. Rowe, Erik Karlsson, Haley Echlin, Ti-Cheng Chang, Lei Wang, Tim van Opijnen, Stanley B. Pounds, Stacey Schultz-Cherry, Jason W. Rosch

Published: May 21, 2019 / DOI: https://doi.org/10.1016/j.chom.2019.04.012

 

Highlights

  • A pneumococcal Tn-seq library was screened in a ferret transmission model
  • The fitness landscape of S. pneumoniae genes during mammalian transmission established
  • Metabolic factors enhance pneumococcal environmental stability
  • Vaccinating dams with identified factors blocks pneumococcal transmission in offspring

 

Summary

The capacity of Streptococcus pneumoniae to successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population.

Keywords: Streptococcus pneumoniae – transmission – ferret – influenza

Keywords: Streptococcus pneumoniae; IPD; Animal models.

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