scholarly journals A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

2015 ◽  
Vol 89 (13) ◽  
pp. 6907-6917 ◽  
Author(s):  
Mariana Baz ◽  
Myeisha Paskel ◽  
Yumiko Matsuoka ◽  
James R. Zengel ◽  
Xing Cheng ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Single Dose ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Virus Vaccine ◽  
Natural Infection ◽  
Influenza Viruses ◽  
Elderly Subjects ◽  
Donor Strain ◽  
Species Barrier

ABSTRACTH3N8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. However, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. A live attenuated, cold-adapted (ca) H3N8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin (HA) and neuraminidase (NA) genes from the A/blue-winged teal/Texas/Sg-00079/2007 (H3N8) (tl/TX/079/07) wt virus and the six internal protein gene segments from thecainfluenza A virus vaccine donor strain, A/Ann Arbor/6/60ca(H2N2), the backbone of the licensed seasonal live attenuated influenza vaccine. One dose of the tl/TX/079/07cavaccine induced a robust neutralizing antibody response against the homologous (tl/TX/079/07) and two heterologous influenza viruses, including the recently emerged A/harbor seal/New Hampshire/179629/2011 (H3N8) and A/northern pintail/Alaska/44228-129/2006 (H3N8) viruses, and conferred robust protection against the homologous and heterologous influenza viruses. We also analyzed human sera against the tl/TX/079/07 H3N8 avian influenza virus and observed low but detectable antibody reactivity in elderly subjects, suggesting that older H3N2 influenza viruses confer some cross-reactive antibody. The latter observation was confirmed in a ferret study. The safety, immunogenicity, and efficacy of the tl/TX/079/07cavaccine in mice and ferrets support further evaluation of this vaccine in humans for use in the event of transmission of an H3N8 avian influenza virus to humans. The human and ferret serology data suggest that a single dose of the vaccine may be sufficient in older subjects.IMPORTANCEAlthough natural infection of humans with an avian H3N8 influenza virus has not yet been reported, this influenza virus subtype has already crossed the species barrier and productively infected mammals. Pandemic preparedness is an important public health priority. Therefore, we generated a live attenuated avian H3N8 vaccine candidate and demonstrated that a single dose of the vaccine was highly immunogenic and protected mice and ferrets against homologous and heterologous H3N8 avian viruses.

scholarly journals The Emergence and Zoonotic Transmission of H10Nx Avian Influenza Virus Infections

mBio ◽  
2021 ◽  
Author(s):  
Holly Everest ◽  
Elizabeth Billington ◽  
Rebecca Daines ◽  
Alice Burman ◽  
Munir Iqbal
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Economic Impact ◽  
Human Health ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Avian Influenza Viruses ◽  
Species Barrier ◽  
Pandemic Threat

Avian influenza viruses pose a continuous threat to both poultry and human health, with significant economic impact. The ability of viruses to reassort and jump the species barrier into mammalian hosts generates a constant pandemic threat.

scholarly journals Swine ANP32A Supports Avian Influenza Virus Polymerase

2020 ◽  
Vol 94 (12) ◽  
Author(s):  
Thomas P. Peacock ◽  
Olivia C. Swann ◽  
Hamish A. Salvesen ◽  
Ecco Staller ◽  
P. Brian Leung ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Virus Replication ◽  
Mammalian Species ◽  
Gene Mutations ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
2009 H1n1 ◽  
Mixing Vessels

ABSTRACT Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as “mixing vessels,” being susceptible to both avian- and human-origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study, we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports the activity of avian-origin influenza virus polymerases and avian influenza virus replication. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic, it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the enhanced proviral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the leucine-rich repeat and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the mixing vessel trait of swine and further our understanding of the evolution and ecology of viruses in this host. IMPORTANCE Avian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but they only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus “mixing vessels.” In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different between swine and humans. Swine ANP32A allows a greater range of influenza viruses, specifically those from birds, to replicate. It does this by binding the virus polymerase more tightly than the human version of the protein. This work helps to explain the unique properties of swine as mixing vessels.

scholarly journals Generation of Live Attenuated Influenza Virus by Using Codon Usage Bias

2015 ◽  
Vol 89 (21) ◽  
pp. 10762-10773 ◽  
Author(s):  
Rebecca L. Y. Fan ◽  
Sophie A. Valkenburg ◽  
Chloe K. S. Wong ◽  
Olive T. W. Li ◽  
John M. Nicholls ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Codon Usage ◽  
Codon Bias ◽  
Seasonal Influenza ◽  
Viral Proteins ◽  
Influenza Viruses ◽  
Donor Strain ◽  
Avian Influenza Viruses ◽  
Attenuated Viruses

ABSTRACTSeasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses with vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells but not in eggs by converting its codon usage so that it is similar to that observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral, and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus, our approach is a successful strategy to generate attenuated viruses for future application as vaccines.IMPORTANCEVaccination has been one of the best protective measures in combating influenza virus infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of the codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern over reverse mutations. The potential use of this kind of codon bias mutant as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza.

scholarly journals Knockout of IRF7 Highlights its Modulator Function of Host Response Against Avian Influenza Virus and the Involvement of MAPK and TOR Signaling Pathways in Chicken

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 385
Author(s):  
Tae Hyun Kim ◽  
Colin Kern ◽  
Huaijun Zhou
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Host Response ◽  
Antiviral Response ◽  
Influenza Viruses ◽  
Interferon Response ◽  
Type I

Interferon regulatory factor 7 (IRF7) is known as the master transcription factor of the type I interferon response in mammalian species along with IRF3. Yet birds only have IRF7, while they are missing IRF3, with a smaller repertoire of immune-related genes, which leads to a distinctive immune response in chickens compared to in mammals. In order to understand the functional role of IRF7 in the regulation of the antiviral response against avian influenza virus in chickens, we generated IRF7-/- chicken embryonic fibroblast (DF-1) cell lines and respective controls (IRF7wt) by utilizing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system. IRF7 knockout resulted in increased viral titers of low pathogenic avian influenza viruses. Further RNA-sequencing performed on H6N2-infected IRF7-/- and IRF7wt cell lines revealed that the deletion of IRF7 resulted in the significant down-regulation of antiviral effectors and the differential expression of genes in the MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) signaling pathways. Dynamic gene expression profiling of the host response between the wildtype and IRF7 knockout revealed potential signaling pathways involving AP1 (activator protein 1), NF-κB (nuclear factor kappa B) and inflammatory cytokines that may complement chicken IRF7. Our findings in this study provide novel insights that have not been reported previously, and lay a solid foundation for enhancing our understanding of the host antiviral response against the avian influenza virus in chickens.

scholarly journals A review of H5Nx avian influenza viruses

2019 ◽  
Vol 7 ◽  
pp. 251513551882162 ◽  
Author(s):  
Ivette A. Nuñez ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Bird Populations ◽  
Pathogenic Avian Influenza ◽  
Pathogenic Avian Influenza Virus

Highly pathogenic avian influenza viruses (HPAIVs), originating from the A/goose/Guangdong/1/1996 H5 subtype, naturally circulate in wild-bird populations, particularly waterfowl, and often spill over to infect domestic poultry. Occasionally, humans are infected with HPAVI H5N1 resulting in high mortality, but no sustained human-to-human transmission. In this review, the replication cycle, pathogenicity, evolution, spread, and transmission of HPAIVs of H5Nx subtypes, along with the host immune responses to Highly Pathogenic Avian Influenza Virus (HPAIV) infection and potential vaccination, are discussed. In addition, the potential mechanisms for Highly Pathogenic Avian Influenza Virus (HPAIV) H5 Reassorted Viruses H5N1, H5N2, H5N6, H5N8 (H5Nx) viruses to transmit, infect, and adapt to the human host are reviewed.

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

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 40 ◽  
Author(s):  
Mengchan Hao ◽  
Shaojie Han ◽  
Dan Meng ◽  
Rong Li ◽  
Jing Lin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Guinea Pigs ◽  
Influenza A ◽  
Reverse Genetics ◽  
Species Barrier ◽  
Airborne Transmission ◽  
H9n2 Subtype ◽  
Influenza A H1n1

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.

scholarly journals The Application of NHEJ-CRISPR/Cas9 and Cre-Lox System in the Generation of Bivalent Duck Enteritis Virus Vaccine against Avian Influenza Virus

Viruses ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 81 ◽  
Author(s):  
Pengxiang Chang ◽  
Yongxiu Yao ◽  
Na Tang ◽  
Jean-Remy Sadeyen ◽  
Joshua Sealy ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Virus Vaccine ◽  
Duck Enteritis Virus ◽  
Enteritis Virus

scholarly journals Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses

2000 ◽  
Vol 74 (3) ◽  
pp. 1443-1450 ◽  
Author(s):  
Jody K. Dybing ◽  
Stacey Schultz-Cherry ◽  
David E. Swayne ◽  
David L. Suarez ◽  
Michael L. Perdue
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Transforming Growth Factor ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Rapid Weight Loss ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic

ABSTRACT In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian influenza viruses were analyzed for their pathogenicity in 6- to 8-week-old BALB/c mice. Both the avian and human HK H5 influenza virus isolates caused severe disease in mice, characterized by induced hypothermia, clinical signs, rapid weight loss, and 75 to 100% mortality by 6 to 8 days postinfection. Three of the non-HK-origin isolates caused no detectable clinical signs. One isolate, A/tk/England/91 (H5N1), induced measurable disease, and all but one of the animals recovered. Infections resulted in mild to severe lesions in both the upper and lower respiratory tracts. Most consistently, the viruses caused necrosis in respiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles with accompanying inflammation. The most severe and widespread lesions were observed in the lungs of HK avian influenza virus-infected mice, while no lesions or only mild lesions were evident with A/ck/Scotland/59 (H5N1) and A/ck/Queretaro/95 (H5N2). The A/ck/Italy/97 (H5N2) and the A/tk/England/91 (H5N1) viruses exhibited intermediate pathogenicity, producing mild to moderate respiratory tract lesions. In addition, infection by the different isolates could be further distinguished by the mouse immune response. The non-HK-origin isolates all induced production of increased levels of active transforming growth factor β following infection, while the HK-origin isolates did not.

scholarly journals Detecting influenza and emerging avian influenza virus by influenza and pneumonia surveillance systems in a large city in China, 2005 to 2016

2019 ◽  
Author(s):  
Xiaorong Guo ◽  
Dong Yang ◽  
Ruchun Liu ◽  
Yaman Li ◽  
Qingqing Hu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Surveillance Systems ◽  
Avian Influenza Viruses ◽  
Influenza A H1n1 ◽  
Death Cases ◽  
Positive Results

Abstract Background: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. This study aimed to analyze the efficiency of two surveillance systems in detecting the emerging avian influenza viruses. Methods: A modified influenza surveillance system (ISS) and a new built pneumonia surveillance system (PSS) have been used to monitor the viruses in Changsha City, China. The ISS is based on monitoring outpatients in two sentinel hospitals to detect mild influenza and avian influenza cases, and PSS is based on monitoring inpatients in all 49 hospitals to detect severe and death influenza cases. Results: During the study period, 3551917 outpatients were monitored by the ISS system, among which 126076 were influenza-like illness (ILI) cases, with the ILI% of 3.55%. Totally, 14913 throat swabs were collected by the ISS system, among which 2016 were tested positive of influenza or avian influenza virus. Among the positive results, 621 were H3N2, 135 were seasonal H1N1, 610 were influenza A/H1N1 (pandemic in 2009), 106 were untyped influenza A, 540 were B, 1 was H5N6, 1 was H7N9, and 2 were H9N2 virus. 5491560 inpatient people were monitored by the PSS system, among which 6.61% (362743/5491560) were pneumonia cases. 10.55% (38260/362743) of reported pneumonia was severe or death cases. 3401 throat swab or lower respiratory tract samples were collected, among which 2094 were tested positive of influenza or avian influenza virus. Among the positive results, 78 were H3N2, 17 were seasonal H1N1, 1871 were influenza A/H1N1, 103 were untyped influenza A, 16 were B, 1 was H5N6, and 8 were H7N9 virus. Of 15 avian influenza cases reported from January, 2005 to September, 2016, 26.7% (4/15) were mild cases detected by the ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. Conclusion: The two systems seem to be of high efficiency in detecting the emerging avian influenza viruses but need to be verified in other cities or countries.

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