H5N1 Influenza Virulence, Pathogenicity and Transmissibility: What do We Know?

Neumann, Gabriele

doi:10.2217/fvl.15.62

Cited by 30 publications

(22 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead, our lab and others have found that the PA segment in the H1N1pdm09 virus contains a number of host-adaptive mutations that determine the activity of vRdRp in mammalian cells [20][21][22]. Additionally, there have been several studies regarding novel H5N1 and H7N9 avian IAVs whose replicative ability and virulence have been linked to mutations in PA in addition to the previously described host adaptive mutations in PB2 [23,24]. Together these studies show that the PA gene segment also plays a major role in the adaptation of avian IAVs to mammals and the emergence of pandemic viruses.…”

Section: Host Adaptive Mutations In Polymerase Proteinsmentioning

confidence: 95%

“…Additionally, the recent outbreaks of highly pathogenic avian IAVs led to identification of previously unknown host adaptive mutations in PA. Characterization of H5N1 viruses, which have caused severe disease in humans, shows that some of these viruses contain the characteristic mutations E627K and D701N in PB2 [23]. However, detailed analysis of H5N1 viruses also revealed the presence of host adaptive mutations in PA.…”

Section: Contribution Of Mutations In Pa To Host Adaptationmentioning

confidence: 99%

See 1 more Smart Citation

Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses

Lutz

Dunagan

Kurebayashi

et al. 2020

Viruses

View full text Add to dashboard Cite

Influenza A viruses (IAVs) are a significant human pathogen that cause seasonal epidemics and occasional pandemics. Avian waterfowl are the natural reservoir of IAVs, but a wide range of species can serve as hosts. Most IAV strains are adapted to one host species and avian strains of IAV replicate poorly in most mammalian hosts. Importantly, IAV polymerases from avian strains function poorly in mammalian cells but host adaptive mutations can restore activity. The 2009 pandemic H1N1 (H1N1pdm09) virus acquired multiple mutations in the PA gene that activated polymerase activity in mammalian cells, even in the absence of previously identified host adaptive mutations in other polymerase genes. These mutations in PA localize within different regions of the protein suggesting multiple mechanisms exist to activate polymerase activity. Additionally, an immunomodulatory protein, PA-X, is expressed from the PA gene segment. PA-X expression is conserved amongst many IAV strains but activity varies between viruses specific for different hosts, suggesting that PA-X also plays a role in host adaptation. Here, we review the role of PA in the emergence of currently circulating H1N1pdm09 viruses and the most recent studies of host adaptive mutations in the PA gene that modulate polymerase activity and PA-X function.

show abstract

Section: Host Adaptive Mutations In Polymerase Proteinsmentioning

confidence: 95%

Section: Contribution Of Mutations In Pa To Host Adaptationmentioning

confidence: 99%

Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses

Lutz

Dunagan

Kurebayashi

et al. 2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Highly Pathogenic Avian Influenza (HPAI) is a highly contagious avian disease, may cause serious economic losses in poultry industry and poses a potential threat to public health (Neumann, 2015). Since the emergence of HPAI virus H5N1 A/goose/Guangdong/1/1996 (GS/GD96) in China in 1996, descendants of this strain continue to spread among avian species and their hemagglutinin (HA) has evolved into multiple distinct phylogenetic clades, subclades and lineages in different geographic locations mainly in Southeast Asia (Smith et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Multiple introductions of reassorted highly pathogenic avian influenza viruses (H5N8) clade 2.3.4.4b causing outbreaks in wild birds and poultry in Egypt

Yehia¹,

Naguib

et al. 2018

Infection, Genetics and Evolution

View full text Add to dashboard Cite

Recently, an increased incidence of outbreaks of highly pathogenic avian influenza (HPAI) H5N8 in poultry linked to infected migratory birds has been reported from different European, Asian and African countries. In Egypt, incursion of HPAI H5N8 virus of clade 2.3.4.4b has been recently registered. Full genomic characterization of 3 virus isolates from wild birds and poultry (backyard and commercial farm sectors) showed high nucleotide similarity among the HA, NA, M, and NS gene segments of the three Egyptian HPAI H5N8 viruses, indicating that they are descendants of a common ancestral virus. However, the analyzed Egyptian H5N8 viruses revealed distinct genotypes involving different origins of the PB2, PB1, PA and/or NP segments. In genotype-1 represented by strain A/common-coot/Egypt/CA285/2016 the PB2 and NP segments showed closest relationship to H5N6 and H6N2 viruses, recently detected in Italy. The second is replacement of PB1 and NP genes A novel reassortant, represented by strain A/duck/Egypt/SS19/2017, showed an exchange of PB1 and NP genes which might have originated from H6N8 or H1N1 and H6N2 viruses. Finally, replacement of PA and NP genes characterized strain A/duck/Egypt/F446/2017. Bayesian phylogeographic analyses revealed that Egyptian H5N8 viruses are highly likely derived from Russian 2016 HPAI H5N8 virus (A/great_crested_grebe/Uvs-Nuur_Lake/341/2016 (H5N8)) and the reassortment likely occurred before incursion to Egypt.

show abstract

“…NS1, PB1-F2, polymerase proteins), the IFN-I response is nonetheless sustained, and its excessive activation during severe illness can lead to increased mortality. Furthermore, during H7N9 and H5N1 severe infections, TGF-β fails to be activated, contributing to increased pathogenicity (69)(70)(71). SARS-CoV-2 stands out from the other β -coronaviruses and influenza A viruses, with a highly perturbed response downstream of Type I IFN signalling, as reflected in the poor balance of measured pro-and anti-inflammatory cytokines (Figures and 4).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 causes a different cytokine response compared to other cytokine storm-causing respiratory viruses in severely ill patients

Ölbei

Hautefort

Módos

et al. 2020

Preprint

View full text Add to dashboard Cite

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS) is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells are activated, and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with COVID-19 for a subgroup of patients. CRS is not unique to SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, H7N9). Here, we collected changing cytokine levels upon infection with the aforementioned viral pathogens through a comprehensive literature search. We analysed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. A map of such responses could help specialists identify interventions that successfully alleviated CRS in different diseases and evaluate whether they could be used in COVID-19 cases.

show abstract

H5N1 Influenza Virulence, Pathogenicity and Transmissibility: What do We Know?

Cited by 30 publications

References 85 publications

Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses

Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses

Multiple introductions of reassorted highly pathogenic avian influenza viruses (H5N8) clade 2.3.4.4b causing outbreaks in wild birds and poultry in Egypt

SARS-CoV-2 causes a different cytokine response compared to other cytokine storm-causing respiratory viruses in severely ill patients

Contact Info

Product

Resources

About