scholarly journals Mammalian ANP32A and ANP32B proteins drive alternative avian influenza virus polymerase adaptations

2020 ◽  
Author(s):  
Thomas. P. Peacock ◽  
Carol M. Sheppard ◽  
Ecco Staller ◽  
Rebecca Frise ◽  
Olivia C. Swann ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Experimental Evolution ◽  
Human Cells ◽  
Influenza Viruses ◽  
Avian Viruses ◽  
Evolution Approach ◽  
Influenza Polymerase

AbstractANP32 proteins, which act as influenza polymerase co-factors, vary between birds and mammals. The well-known mammalian adaptation, PB2-E627K, enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbour this adaptation. Here, we show that alternative PB2 adaptations, Q591R and D701N also allow influenza polymerase to use mammalian ANP32 proteins. PB2-E627K strongly favours use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs and horses where ANP32A proteins are more strongly pro-viral. In an experimental evolution approach, passage of avian viruses in human cells drives acquisition of PB2-E627K, but not when ANP32B is ablated. The strong pro-viral support of ANP32B for PB2-E627K maps to the LCAR region of ANP32B.

scholarly journals Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Bartram L. Smith ◽  
Guifang Chen ◽  
Claus O. Wilke ◽  
Robert M. Krug
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Codon Usage ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
Human Cells ◽  
Influenza Viruses ◽  
Human Adaptation ◽  
Influenza A Viruses ◽  
Avian Influenza Viruses

ABSTRACTInfluenza A viruses cause an annual contagious respiratory disease in humans and are responsible for periodic high-mortality human pandemics. Pandemic influenza A viruses usually result from the reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to adapt to humans. Here we focus on the human adaptation of the synonymous codons of the avian influenza virus PB1 gene of the 1968 H3N2 pandemic virus. We generated recombinant H3N2 viruses differing only in codon usage of PB1 mRNA and demonstrated that codon usage of the PB1 mRNA of recent H3N2 virus isolates enhances replication in interferon (IFN)-treated human cells without affecting replication in untreated cells, thereby partially alleviating the interferon-induced antiviral state. High-throughput sequencing of tRNA pools explains the reduced inhibition of replication by interferon: the levels of some tRNAs differ between interferon-treated and untreated human cells, and evolution of the codon usage of H3N2 PB1 mRNA is skewed toward interferon-altered human tRNA pools. Consequently, the avian influenza virus-derived PB1 mRNAs of modern H3N2 viruses have acquired codon usages that better reflect tRNA availabilities in IFN-treated cells. Our results indicate that the change in tRNA availabilities resulting from interferon treatment is a previously unknown aspect of the antiviral action of interferon, which has been partially overcome by human-adapted H3N2 viruses.IMPORTANCEPandemic influenza A viruses that cause high human mortality usually result from reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to adapt to humans. Here we focus on the human adaptation of the avian influenza virus PB1 gene that was incorporated into the 1968 H3N2 pandemic virus. We demonstrate that the coding sequence of the PB1 mRNA of modern H3N2 viruses enhances replication in human cells in which interferon has activated a potent antiviral state. Reduced interferon inhibition results from evolution of PB1 mRNA codons skewed toward the pools of tRNAs in interferon-treated human cells, which, as shown here, differ significantly from the tRNA pools in untreated human cells. Consequently, avian influenza virus-derived PB1 mRNAs of modern H3N2 viruses have acquired codon usages that better reflect tRNA availabilities in IFN-treated cells and are translated more efficiently.

scholarly journals Receptor Binding Profiles of Avian Influenza Virus Hemagglutinin Subtypes on Human Cells as a Predictor of Pandemic Potential

2010 ◽  
Vol 85 (4) ◽  
pp. 1875-1880 ◽  
Author(s):  
H. Shelton ◽  
G. Ayora-Talavera ◽  
J. Ren ◽  
S. Loureiro ◽  
R. J. Pickles ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Receptor Binding ◽  
Human Cells ◽  
Influenza Virus Hemagglutinin

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 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 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 Evidence for Avian and Human Host Cell Factors That Affect the Activity of Influenza Virus Polymerase

2010 ◽  
Vol 84 (19) ◽  
pp. 9978-9986 ◽  
Author(s):  
Olivier Moncorgé ◽  
Manuela Mura ◽  
Wendy S. Barclay
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Host Range ◽  
Influenza A ◽  
Human Cells ◽  
Influenza A Viruses ◽  
New Host ◽  
Range Restriction ◽  
Positive Factor

ABSTRACT Typical avian influenza A viruses do not replicate efficiently in humans. The molecular basis of host range restriction and adaptation of avian influenza A viruses to a new host species is still not completely understood. Genetic determinants of host range adaptation have been found on the polymerase complex (PB1, PB2, and PA) as well as on the nucleoprotein (NP). These four viral proteins constitute the minimal set for transcription and replication of influenza viral RNA. It is widely documented that in human cells, avian-derived influenza A viral polymerase is poorly active, but despite extensive study, the reason for this blockade is not known. We monitored the activity of influenza A viral polymerases in heterokaryons formed between avian (DF1) and human (293T) cells. We have discovered that a positive factor present in avian cells enhances the activity of the avian influenza virus polymerase. We found no evidence for the existence of an inhibitory factor for avian virus polymerase in human cells, and we suggest, instead, that the restriction of avian influenza virus polymerases in human cells is the consequence of the absence or the low expression of a compatible positive cofactor. Finally, our results strongly suggest that the well-known adaptative mutation E627K on viral protein PB2 facilitates the ability of a human positive factor to enhance replication of influenza virus in human cells.

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.

scholarly journals The Impact of Migratory Flyways on the Spread of Avian Influenza Virus in North America

2016 ◽  
Author(s):  
Mathieu Fourment ◽  
Aaron E. Darling ◽  
Edward C. Holmes
Keyword(s):  
Influenza Virus ◽  
Genetic Structure ◽  
North America ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Bird Species ◽  
Influenza Viruses ◽  
Data Sets ◽  
Avian Influenza Viruses ◽  
The Impact

AbstractWild birds are the major reservoir hosts for influenza A viruses (AIVs) and have been implicated in the emergence of pandemic events in livestock and human populations. Understanding how AIVs spread within and across continents is therefore critical to the development of successful strategies to manage and reduce the impact of influenza outbreaks. In North America many bird species undergo seasonal migratory movements along a North-South axis, thereby fostering opportunities for viruses to spread over long distances. However, the role played by such avian flyways in shaping the genetic structure of AIV populations has proven controversial. To assess the relative contribution of bird migration along flyways to the genetic structure of AIV we performed a large-scale phylogeographic study of viruses sampled in the USA and Canada, involving the analysis of 3805 to 4505 sequences from 36 to 38 geographic localities depending on the gene data set. To assist this we developed a maximum likelihood-based genetic algorithm to explore a wide range of complex spatial models, thereby depicting a more complete picture of the migration network than previous studies. Based on phylogenies estimated from nucleotide data sets, our results show that AIV migration rates within flyways are significantly higher than those between flyways, indicating that the migratory patterns of birds play a key role in pathogen dispersal. These findings provide valuable insights into the evolution, maintenance and transmission of AIVs, in turn allowing the development of improved programs for surveillance and risk assessment.Significance StatementAvian influenza viruses infect a wide variety of wild bird species and represent a potential disease threat to the poultry industry and hence to human and livestock populations. However, the ecological factors that drive the geographic spread and evolution of these viruses are both poorly understood and controversial at the continental scale, particularly the role played by migratory flyways in shaping patterns of virus dispersal. Using a novel phylogeographic analysis of large genomic data sets we show migration flyways act as important transmission barriers to the spread of avian influenza viruses in North America. Hence, these results indicate that the spread of avian influenza virus in wild birds in North America has an element of predictability.

scholarly journals Overview of the Epizootiological Situation on Highly Pathogenic Avian Influenza Virus in Russia in 2019

2020 ◽  
pp. 31-37
Author(s):  
V. Yu. Marchenko ◽  
N. I. Goncharova ◽  
Thi Nhai Tran ◽  
Khac Sau Trinh ◽  
Ngoc Quyen Nguyen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Saratov Region ◽  
Pathogenic Avian Influenza ◽  
Virus Surveillance ◽  
Pathogenic Avian Influenza Virus

This review describes the current situation on highly pathogenic avian influenza virus in 2019 and predicts the possible further spread of avian influenza in Russia. In 2019 outbreaks were reported among wild birds and poultry, as well as human infections with influenza viruses of the subtypes H5Nx, H7N9 and H9N2 in several countries. In 2019, only two outbreaks of highly pathogenic avian influenza H5N8 in Russia occurred. Both outbreaks were recorded in January at poultry farm in the Rostov Region. In addition, in May 2019 avian influenza virus of H14N7 subtype was isolated from a wild bird during the avian influenza virus surveillance in Tomsk Region. In June 2019, a strain of H13N2 subtype was isolated in the territory of Kamchatka Region, then, in August 2019, an influenza virus of H13N6 subtype was isolated in the Saratov Region. It was revealed that some strains of avian influenza virus isolated in Russia have a high degree of identity with strains circulating in South-East Asia. This was shown by the phylogenetic analysis of A/ H5Nx influenza viruses previously isolated in the Saratov Region and the Socialist Republic of Vietnam during the avian influenza virus surveillance. Thus, it was demonstrated again that the territory of Russia plays a key geographical role in the global spread of avian influenza virus.

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