The #PA #Subunit of the #Influenza Virus #Polymerase Complex Affects #Replication and #Airborne #Transmission of the #H9N2 Subtype #Avian Influenza Virus (Viruses, abstract)

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

Viruses. 2019 Jan 9;11(1). pii: E40. doi: 10.3390/v11010040.

The PA Subunit of the Influenza Virus Polymerase Complex Affects Replication and Airborne Transmission of the H9N2 Subtype Avian Influenza Virus.

Hao M1,2, Han S3,4, Meng D5,6, Li R7, Lin J8, Wang M9, Zhou T10, Chai T11.

Author information: 1 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. mengchan1993@126.com. 2 Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Taian 270016, China. mengchan1993@126.com. 3 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 18763896230@163.com. 4 Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Taian 270016, China. 18763896230@163.com. 5 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. iamli_z@126.com. 6 Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Taian 270016, China. iamli_z@126.com. 7 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. lirong19900129@163.com. 8 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 18763806701@163.com. 9 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 18854937499@163.com. 10 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 13864453175@163.com. 11 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. chaitj117@163.com.

 

Abstract

The polymerase acidic (PA) protein is the third subunit of the influenza A virus polymerase. In recent years, studies have shown that PA plays an important role in overcoming the host species barrier and host adaptation of the avian influenza virus (AIV). The objective of this study was to elucidate the role of the PA subunit on the replication and airborne transmission of the H9N2 subtype AIV. By reverse genetics, a reassortant rSD01-PA was derived from the H9N2 subtype AIV A/Chicken/Shandong/01/2008 (SD01) by introducing the PA gene from the pandemic influenza A H1N1 virus A/swine/Shandong/07/2011 (SD07). Specific pathogen-free (SPF) chickens and guinea pigs were selected as the animal models for replication and aerosol transmission studies. Results show that rSD01-PA lost the ability of airborne transmission among SPF chickens because of the single substitution of the PA gene. However, rSD01-PA could infect guinea pigs through direct contact, while the parental strain SD01 could not, even though the infection of rSD01-PA could not be achieved through aerosol. In summary, our results indicate that the protein encoded by the PA gene plays a key role in replication and airborne transmission of the H9N2 subtype AIV.

KEYWORDS: H9N2 AIV; airborne transmission; pandemic 2009 H1N1 virus; reassortment; replication

PMID: 30634394 PMCID: PMC6356911 DOI: 10.3390/v11010040 [Indexed for MEDLINE]  Free PMC Article

Keywords: Avian Influenza; Swine Influenza; H1N1; H9N2; Reassortant strain.

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#Text-Based #Illness #Monitoring for #Detection of Novel Influenza A Virus Infections During an #Influenza A #H3N2v Virus #Outbreak in #Michigan, 2016: #Surveillance and Survey (JMIR Public Health Surveill., abstract)

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

JMIR Public Health Surveill. 2019 Apr 26;5(2):e10842. doi: 10.2196/10842.

Text-Based Illness Monitoring for Detection of Novel Influenza A Virus Infections During an Influenza A (H3N2)v Virus Outbreak in Michigan, 2016: Surveillance and Survey.

Stewart RJ1,2, Rossow J3,4, Eckel S5, Bidol S5, Ballew G6, Signs K5, Conover JT7, Burns E1, Bresee JS1, Fry AM1, Olsen SJ1, Biggerstaff M1.

Author information: 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States. 2 Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA, United States. 3 Epidemiology Elective Program, Division of Scientific Education and Professional Development, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, United States. 4 College of Veterinary Medicine, University of Georgia, Athens, GA, United States. 5 Michigan Department of Health and Human Services, Lansing, MI, United States. 6 Compliant Campaign, Scottsdale, AZ, United States. 7 Michigan State University Extension, East Lansing, MI, United States.

 

Abstract

BACKGROUND:

Rapid reporting of human infections with novel influenza A viruses accelerates detection of viruses with pandemic potential and implementation of an effective public health response. After detection of human infections with influenza A (H3N2) variant (H3N2v) viruses associated with agricultural fairs during August 2016, the Michigan Department of Health and Human Services worked with the US Centers for Disease Control and Prevention (CDC) to identify infections with variant influenza viruses using a text-based illness monitoring system.

OBJECTIVE:

To enhance detection of influenza infections using text-based monitoring and evaluate the feasibility and acceptability of the system for use in future outbreaks of novel influenza viruses.

METHODS:

During an outbreak of H3N2v virus infections among agricultural fair attendees, we deployed a text-illness monitoring (TIM) system to conduct active illness surveillance among households of youth who exhibited swine at fairs. We selected all fairs with suspected H3N2v virus infections. For fairs without suspected infections, we selected only those fairs that met predefined criteria. Eligible respondents were identified and recruited through email outreach and/or on-site meetings at fairs. During the fairs and for 10 days after selected fairs, enrolled households received daily, automated text-messages inquiring about illness; reports of illness were investigated by local health departments. To understand the feasibility and acceptability of the system, we monitored enrollment and trends in participation and distributed a Web-based survey to households of exhibitors from five fairs.

RESULTS:

Among an estimated 500 households with a member who exhibited swine at one of nine selected fairs, representatives of 87 (17.4%) households were enrolled, representing 392 household members. Among fairs that were ongoing when the TIM system was deployed, the number of respondents peaked at 54 on the third day of the fair and then steadily declined throughout the rest of the monitoring period; 19 out of 87 household representatives (22%) responded through the end of the 10-day monitoring period. We detected 2 H3N2v virus infections using the TIM system, which represents 17% (2/12) of all H3N2v virus infections detected during this outbreak in Michigan. Of the 70 survey respondents, 16 (23%) had participated in the TIM system. A total of 73% (11/15) participated because it was recommended by fair coordinators and 80% (12/15) said they would participate again.

CONCLUSIONS:

Using a text-message system, we monitored for illness among a large number of individuals and households and detected H3N2v virus infections through active surveillance. Text-based illness monitoring systems are useful for detecting novel influenza virus infections when active monitoring is necessary. Participant retention and testing of persons reporting illness are critical elements for system improvement.

©Rebekah J Stewart, John Rossow, Seth Eckel, Sally Bidol, Grant Ballew, Kimberly Signs, Julie Thelen Conover, Erin Burns, Joseph S Bresee, Alicia M Fry, Sonja J Olsen, Matthew Biggerstaff. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.04.2019.

KEYWORDS: agricultural; fairs; influenza; novel; surveillance; texting

PMID: 31025948 DOI: 10.2196/10842

Keywords: Swine Influenza; H3N2v; Michigan; USA; Society.

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#Virus #survival and fitness when multiple genotypes and subtypes of #influenza A viruses exist and circulate in #swine (Virology, abstract)

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

Virology. 2019 Apr 9;532:30-38. doi: 10.1016/j.virol.2019.03.016. [Epub ahead of print]

Virus survival and fitness when multiple genotypes and subtypes of influenza A viruses exist and circulate in swine.

Ma J1, Shen H1, McDowell C1, Liu Q1, Duff M1, Lee J1, Lang Y1, Hesse D1, Richt JA1, Ma W2.

Author information: 1 Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA. 2 Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA. Electronic address: wjma@ksu.edu.

 

Abstract

We performed swine influenza virus (SIV) surveillance in Midwest USA and isolated 100 SIVs including endemic and reassortant H1 and H3 viruses with 2009 pandemic H1N1 genes. To determine virus evolution when different genotypes and subtypes of influenza A viruses circulating in the same swine herd, a virus survival experiment was conducted in pigs mimicking field situations. Five different SIVs were used to infect five pigs individually, then two groups of sentinel pigs were introduced to investigate virus transmission. Results showed that each virus replicated efficiently in lungs of each infected pig, but only reassortant H3N2 and H1N2v viruses transmitted to the primary contact pigs. Interestingly, the parental H1N2v was the majority of virus detected in the second group of sentinel pigs. These data indicate that the H1N2v seems to be more viable in swine herds than other SIV genotypes, and reassortment can enhance viral fitness and transmission.

Copyright © 2019. Published by Elsevier Inc.

KEYWORDS: H1N2v; Pigs; Surveillance; Swine influenza virus; Virus competition and survival

PMID: 31003122 DOI: 10.1016/j.virol.2019.03.016

Keywords: Influenza A; Swine Influenza; Pigs; H1N1; H3N2; H1N2.

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#Interferon as a #Mucosal #Adjuvant for an #Influenza #Vaccine in #Pigs (Virol Sin., abstract)

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

Interferon as a Mucosal Adjuvant for an Influenza Vaccine in Pigs

Authors: Lirong Liu, Wenhui Fan, He Zhang, Shuang Zhang, Liang Cui, Meng Wang, Xiaoyuan Bai, Wenxian Yang, Lei Sun, Limin Yang, Wenjun Liu, Jing Li

RESEARCH ARTICLE / First Online: 15 April 2019

 

Abstract

Interferon, a natural protein that is produced by a variety of cells during viral infection, activates the transcription of multiple functional genes in cells, regulates synergy among various signaling pathways, and mediates many biological functions such as antiviral activity, immune regulation, and cell growth. However, clinical research on interferon in livestock is lacking. In this study, recombinant porcine interferon (PoIFNα) was used as an adjuvant, in combination with inactivated influenza virus, to vaccinate 6-week-old pigs via nasal infusion. The transcription of target genes was then monitored and the functions of PoIFNα were determined with respect to the activation of mucosal immunity. We found that a combination of low-dose PoIFNα and inactivated influenza virus could significantly up-regulate the expression of immunoregulatory cytokines such as IL-2, IL-18, IFN-γ, IL-6, and IL-10 by real-time PCR, suggesting the induction of a strong mucosal innate immune response after administration. In addition, low-dose PoIFNα can significant enhancing the transcription of genes encoding homing factors including CCR9 and CCR10 (P < 0.001), thereby resulting in the induction of higher levels of HA-specific antibodies (P < 0.05), which can be determined by ELISA and IFA. Post-immunization challenges with H1N1 virus demonstrated that PoIFNα, combined with inactivated influenza virus, could alleviate clinical signs in pigs during the early stages of viral infection. These studies reveal low-dose PoIFNα as a potential mucosal adjuvant for influenza virus in pigs.

Keywords: Porcine interferon α (PoIFNα) – H1N1 – influenza virus – Intranasal administration – Cytokines

 

Electronic supplementary material

The online version of this article ( https://doi.org/10.1007/s12250-019-00102-7) contains supplementary material, which is available to authorized users.
Notes

Acknowledgements

We gratefully acknowledge the workers of Beijing Sinder Technology Co., Ltd. for their help with pig immunization and sample collection. This work was supported by Grants from the National Key R&D Programme of China (2017YFD051105), the National Natural Science Foundation of China (31630079), the National Science and Technology Major Project (2018ZX10101004), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010000). W.J.L. is the principal investigator of the Innovative Research Group of the National Natural Science Foundation of China (Grant No. 81621091). J.L. is supported by Youth Innovation Promotion Association of CAS (2019).

Author Contributions

JL and WL supervised the Project and designed the study; JL and LL planned and conducted the experimental work, analyzed the data, and wrote the manuscript; WF, HZ, SZ, LC, MW, XB, WY, LY, and LS provided technical support. All authors read and approved the final manuscript.

 

Compliance with Ethical Standards

Conflicts of interest

All authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The pig experimental design and protocols used in this study were approved by the Institute of Microbiology, Chinese Academy of Sciences of Research Ethics Committee (Permit Number: PZIMCAS2017001). All pig experimental procedures were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of People’s Republic of China.

Keywords: Influenza A; Swine Influenza; H1N1; Pigs; Vaccines; Interferons.

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What Are the #Transmission #Mechanisms of #Influenza A Viruses in Wild #Mammals? (J Infect Dis., summary)

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

What Are the Transmission Mechanisms of Influenza A Viruses in Wild Mammals?

J Jeffrey Root

The Journal of Infectious Diseases, jiz033, https://doi.org/10.1093/infdis/jiz033

Published: 06 March 2019

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Some influenza A viruses (IAVs) represent serious potential threats to public and agricultural health, with 3 notable examples from the past decade. During 2009, a novel H1N1 IAV (A[H1N1]pdm09), which was first detected in the United States, spread rapidly throughout many regions of the world [1]. In the United States alone, the Centers for Disease Control and Prevention estimated that >60 million human cases were associated with this emergent and pandemic virus [1]. During 2013, a novel H7N9 avian-origin IAV (Asian lineage avian influenza A[H7N9] virus) was first detected in China. This virus not only cost the poultry industry more than $1 billion through culling and market closures, it also proved to be detrimental to public health, as this virus is readily transmitted to humans and can cause moderate-to-high rates of mortality [2, 3]. More recently, a highly pathogenic clade 2.3.4.4 avian IAV was first detected in North America during 2014. Ultimately, the introduction of this virus (and subsequent reassortant viruses) elicited the most expensive highly pathogenic IAV outbreak in US history [4], with total losses estimated to be billions of dollars [5]. These 3 examples exemplify the enormous burdens that some IAVs can place on public and agricultural health systems and suggest that a diversity of studies need to be conducted to address the complex epidemiology of these virus-host systems.

(…)

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Notes

Financial support. This work was supported by the US Department of Agriculture.

Potential conflicts of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords: Influenza A; Wildlife; Wild birds.

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Sowing the #Seeds of a #Pandemic? #Mammalian #Pathogenicity and Transmissibility of #H1 Variant #Influenza Viruses from the #Swine Reservoir (Trop Med Infect Dis., abstract)

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

Trop Med Infect Dis. 2019 Feb 27;4(1). pii: E41. doi: 10.3390/tropicalmed4010041.

Sowing the Seeds of a Pandemic? Mammalian Pathogenicity and Transmissibility of H1 Variant Influenza Viruses from the Swine Reservoir.

Pulit-Penaloza JA1, Belser JA2, Tumpey TM3, Maines TR4.

Author information: 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. jpulitpenaloza@cdc.gov. 2 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. jax6@cdc.gov. 3 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. tft9@cdc.gov. 4 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. zay9@cdc.gov.

 

Abstract

Emergence of genetically and antigenically diverse strains of influenza to which the human population has no or limited immunity necessitates continuous risk assessments to determine the likelihood of these viruses acquiring adaptations that facilitate sustained human-to-human transmission. As the North American swine H1 virus population has diversified over the last century by means of both antigenic drift and shift, in vivo assessments to study multifactorial traits like mammalian pathogenicity and transmissibility of these emerging influenza viruses are critical. In this review, we examine genetic, molecular, and pathogenicity and transmissibility data from a panel of contemporary North American H1 subtype swine-origin viruses isolated from humans, as compared to H1N1 seasonal and pandemic viruses, including the reconstructed 1918 virus. We present side-by-side analyses of experiments performed in the mouse and ferret models using consistent experimental protocols to facilitate enhanced interpretation of in vivo data. Contextualizing these analyses in a broader context permits a greater appreciation of the role that in vivo risk assessment experiments play in pandemic preparedness. Collectively, we find that despite strain-specific heterogeneity among swine-origin H1 viruses, contemporary swine viruses isolated from humans possess many attributes shared by prior pandemic strains, warranting heightened surveillance and evaluation of these zoonotic viruses.

KEYWORDS: ferret; influenza; mouse; pandemic; swine; variant

PMID: 30818793 DOI: 10.3390/tropicalmed4010041

Keywords: Influenza A; H1N1; H3N2; Pigs; Pandemic Influenza.

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Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in #pigs after a heterosubtypic #influenza virus Sw #H3N2 challenge (PLoS One, abstract)

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

PLoS One. 2019 Mar 1;14(3):e0212431. doi: 10.1371/journal.pone.0212431. eCollection 2019.

Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge.

Sisteré-Oró M1, Vergara-Alert J1, Stratmann T2, López-Serrano S1, Pina-Pedrero S1, Córdoba L1, Pérez-Maillo M1, Pleguezuelos P1, Vidal E1, Veljkovic V3, Segalés J4,5, Nielsen J6, Fomsgaard A6, Darji A1.

Author information: 1 IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. 2 Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain. 3 Centre for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, Belgrade, Serbia. 4 UAB, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. 5 Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain. 6 Virus Research and Development Laboratory, Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen S, Denmark.

 

Abstract

Swine influenza viruses (SIVs), the causal agents of swine influenza, are not only important to control due to the economic losses in the swine industry, but also can be pandemic pathogens. Vaccination is one of the most relevant strategies to control and prevent influenza infection. Current human vaccines against influenza induce strain-specific immunity and annual update is required due to the virus antigenic shift phenomena. Previously, our group has reported the use of conserved hemagglutinin peptides (HA-peptides) derived from H1-influenza virus as a potential multivalent vaccine candidate. Immunization of swine with these HA-peptides elicited antibodies that recognized and neutralized heterologous influenza viruses in vitro and demonstrated strong hemagglutination-inhibiting activity. In the present work, we cloned one HA-peptide (named NG34) into a plasmid fused with cytotoxic T lymphocyte-associated antigen (CTLA4) which is a molecule that modifies T cell activation and with an adjuvant activity interfering with the adaptive immune response. The resulting plasmid, named pCMV-CTLA4-Ig-NG34, was administered twice to animals employing a needle-free delivery approach. Two studies were carried out to test the efficacy of pCMV-CTLA4-Ig-NG34 as a potential swine influenza vaccine, one in seronegative and another in seropositive pigs against SIV. The second one was aimed to evaluate whether pCMV-CTLA4-Ig-NG34 vaccination would overcome maternally derived antibodies (MDA). After immunization, all animals were intranasally challenged with an H3N2 influenza strain. A complete elimination or significant reduction in the viral shedding was observed within the first week after the challenge in the vaccinated animals from both studies. In addition, no challenged heterologous virus load was detected in the airways of vaccinated pigs. Overall, it is suggested that the pCMV-CTLA4-Ig-NG34 vaccine formulation could potentially be used as a multivalent vaccine against influenza viruses.

PMID: 30822308 DOI: 10.1371/journal.pone.0212431

Keywords: Swine Influenza; H3N2; Pigs; Vaccines.

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