| 1. |
- Mueller, Ralf C., et al.
(författare)
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A high-quality genome and comparison of short-versus long-read transcriptome of the palaearctic duck Aythya fuligula (tufted duck)
- 2021
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The tufted duck is a non-model organism that experiences high mortality in highly pathogenic avian influenza outbreaks. It belongs to the same bird family (Anatidae) as the mallard, one of the best-studied natural hosts of low-pathogenic avian influenza viruses. Studies in non-model bird species are crucial to disentangle the role of the host response in avian influenza virus infection in the natural reservoir. Such endeavour requires a high-quality genome assembly and transcriptome.Findings: This study presents the first high-quality, chromosome-level reference genome assembly of the tufted duck using the Vertebrate Genomes Project pipeline. We sequenced RNA (complementary DNA) from brain, ileum, lung, ovary, spleen, and testis using Illumina short-read and Pacific Biosciences long-read sequencing platforms, which were used for annotation. We found 34 autosomes plus Z and W sex chromosomes in the curated genome assembly, with 99.6% of the sequence assigned to chromosomes. Functional annotation revealed 14,099 protein-coding genes that generate 111,934 transcripts, which implies a mean of 7.9 isoforms per gene. We also identified 246 small RNA families.Conclusions: This annotated genome contributes to continuing research into the host response in avian influenza virus infections in a natural reservoir. Our findings from a comparison between short-read and long -read reference transcriptomics contribute to a deeper understanding of these competing options. In this study, both technologies complemented each other. We expect this annotation to be a foundation for further comparative and evolutionary genomic studies, including many waterfowl relatives with differing susceptibilities to avian influenza viruses.
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| 2. |
- Atterby, Clara, et al.
(författare)
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The Potential of Isolation Source to Predict Colonization in Avian Hosts : A Case Study in Campylobacter jejuni Strains From Three Bird Species
- 2018
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter jejuni is the primary cause of bacterial gastroenteritis worldwide, infecting humans mostly through consumption of contaminated poultry. C. jejuni is common in the gut of wild birds, and shows distinct strain-specific association to particular bird species. This contrasts with farm animals, in which several genotypes co-exist. It is unclear if the barriers restricting transmission between host species of such specialist strains are related to environmental factors such as contact between host species, bacterial survival in the environment, etc., or rather to strain specific adaptation to the intestinal environment of specific hosts. We compared colonization dynamics in vivo between two host-specific C. jejuni from a song thrush (ST-1304 complex) and a mallard (ST-995), and a generalist strain from chicken (ST-21 complex) in a wild host, the mallard (Anas platyrhynchos). In 18-days infection experiments, the song thrush strain showed only weak colonization and was cleared from all birds after 10 days, whereas both mallard and chicken strains remained stable. When the chicken strain was given 4 days prior to co-infection of the same birds with a mallard strain, it was rapidly outcompeted by the latter. In contrast, when the mallard strain was given 4 days prior to co-infection with the chicken strain, the mallard strain remained and expansion of the chicken strain was delayed. Our results suggest strain-specific differences in the ability of C. jejuni to colonize mallards, likely associated with host origin. This difference might explain observed host association patterns in C. jejuni from wild birds.
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| 3. |
- Eriksson, Per, et al.
(författare)
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Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species - Support for the Community Concept
- 2019
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Avian influenza A viruses (AIVs) have a broad host range, but are most intimately associated with waterfowl (Anseriformes) and, in the case of the H13 and H16 subtypes, gulls (Charadriiformes). Host associations are multifactorial, but a key factor is the ability of the virus to bind host cell receptors and thereby initiate infection. The current study aims at investigating the tissue attachment pattern of a panel of AIVs, comprising H3N2, H6N1, H12N5, and H16N3, to avian trachea and colon tissue samples obtained from host species of different orders. Virus attachment was not restricted to the bird species or order from which the virus was isolated. Instead, extensive virus attachment was observed to several distantly related avian species. In general, more virus attachment and receptor expression were observed in trachea than in colon samples. Additionally, a human seasonal H3N2 virus was studied. Unlike the studied AIVs, this virus mainly attached to tracheae from Charadriiformes and a very limited set of avian cola. In conclusion, the reported results highlight the importance of AIV attachment to trachea in many avian species. Finally, the importance of chickens and mallards in AIVs dynamics was illustrated by the abundant AIV attachment observed.
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| 4. |
- Helin, Anu S., et al.
(författare)
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A rapid and transient innate immune response to avian influenza infection in mallards
- 2018
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Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 95, s. 64-72
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Tidskriftsartikel (refereegranskat)abstract
- The vertebrate innate immune system provides hosts with a rapid, non-specific response to a wide range of invading pathogens. However, the speed and duration of innate responses will be influenced by the co-evolutionary dynamics of specific host-pathogen combinations. Here, we show that low pathogenic avian influenza virus (LPAI) subtype H1N1 elicits a strong but extremely transient innate immune response in its main wildlife reservoir, the mallard (Anas platyrhynchos). Using a series of experimental and methodological improvements over previous studies, we followed the expression of retinoic acid inducible gene 1 (RIG-I) and myxovirus resistance gene (Mx) in mallards semi-naturally infected with low pathogenic H1N1. One day post infection, both RIG-I and Mx were significantly upregulated in all investigated tissues. By two days post infection, the expression of both genes had generally returned to basal levels, and remained so for the remainder of the experiment. This is despite the fact that birds continued to actively shed viral particles throughout the study period. We additionally show that the spleen plays a particularly active role in the innate immune response to LPAI. Waterfowl and avian influenza viruses have a long co-evolutionary history, suggesting that the mallard innate immune response has evolved to provide a minimum effective response to LPAIs such that the viral infection is brought under control while minimising the damaging effects of a sustained immune response.
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| 5. |
- Helin, Anu S., et al.
(författare)
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Expression of immune genes RIG-I and Mx in mallard ducks infected with low pathogenic avian influenza (LPAI) : A dataset
- 2018
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Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 18, s. 1562-1566
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Tidskriftsartikel (refereegranskat)abstract
- This article provides data on primer sequences used to amplify the innate immune genes RIG-I and Mx and a set of normalizing reference genes in mallards (Anal platyrhynchos), and shows which reference genes are stable, per tissue, for our experimental settings. Data on the expressional changes of these two genes over a time-course of infection with low pathogenic avian influenza virus (LPAI) are provided. Individual-level data are also presented, including LPAI infection load, and per tissue gene expression of RIG-I and Mx. Gene expression in two outlier individuals is explored in more depth. (C) 2018 The Authors. Published by Elsevier Inc.
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| 6. |
- Naguib, Mahmoud, et al.
(författare)
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A Comparison of Host Responses to Infection with Wild-Type Avian Influenza Viruses in Chickens and Tufted Ducks
- 2023
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Cross-species transmission of influenza A virus (IAV) from wild waterfowl to poultry is the first step in a chain of events that can ultimately lead to exposure and infection of humans. Herein, we study the outcome of infection with eight different mallard-origin IAV subtypes in two different avian hosts: tufted ducks and chickens. We found that infection and shedding patterns as well as innate immune responses were highly dependent on viral subtypes, host species, and inoculation routes. For example, intraoesophageal inoculation, commonly used in mallard infection experiments, resulted in no infections in contrast to oculonasal inoculation, suggesting a difference in transmission routes. Despite H9N2 being endemic in chickens, inoculation of mallard-origin H9N2 failed to cause viable infection beyond 1 day postinfection in our study design. The innate immune responses were markedly different in chickens and tufted ducks, and despite the presence of retinoic acid-inducible gene-I (RIG-I) in tufted duck transcriptomes, it was neither up nor downregulated in response to infection. Overall, we have revealed the heterogeneity of infection patterns and responses in two markedly different avian hosts following a challenge with mallard-origin IAV. These virus-host interactions provide new insights into important aspects of interspecies transmission of IAV.IMPORTANCE Our current findings highlight important aspects of IAV infection in birds that have implications for our understanding of its zoonotic ecology. In contrast to mallards where the intestinal tract is the main site of IAV replication, chickens and tufted ducks show limited or no signs of intestinal infection suggesting that the fecal-oral transmission route might not apply to all bird IAV host species. Our results indicate that mallard-origin IAVs undergo genetic changes upon introduction into new hosts, suggesting rapid adaptation to a new environment. However, similar to the mallard, chickens and tufted ducks show a limited immune response to infection with low pathogenic avian influenza viruses. These findings and future studies in different IAV hosts are important for our understanding of barriers to IAV transmission between species and ultimately from the wild reservoir to humans. Our current findings highlight important aspects of IAV infection in birds that have implications for our understanding of its zoonotic ecology. In contrast to mallards where the intestinal tract is the main site of IAV replication, chickens and tufted ducks show limited or no signs of intestinal infection suggesting that the fecal-oral transmission route might not apply to all bird IAV host species.
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| 7. |
- Ramey, Andrew M., et al.
(författare)
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Antibiotic-Resistant Escherichia coli in Migratory Birds Inhabiting Remote Alaska
- 2018
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Ingår i: EcoHealth. - : Springer. - 1612-9202 .- 1612-9210. ; 15:1, s. 72-81
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Tidskriftsartikel (refereegranskat)abstract
- We explored the abundance of antibiotic-resistant Escherichia coli among migratory birds at remote sites in Alaska and used a comparative approach to speculate on plausible explanations for differences in detection among species. At a remote island site, we detected antibiotic-resistant E. coli phenotypes in samples collected from glaucous-winged gulls (Larus glaucescens), a species often associated with foraging at landfills, but not in samples collected from black-legged kittiwakes (Rissa tridactyla), a more pelagic gull that typically inhabits remote areas year-round. We did not find evidence for antibiotic-resistant E. coli among 347 samples collected primarily from waterfowl at a second remote site in western Alaska. Our results provide evidence that glaucous-winged gulls may be more likely to be infected with antibiotic-resistant E. coli at remote breeding sites as compared to sympatric black-legged kittiwakes. This could be a function of the tendency of glaucous-winged gulls to forage at landfills where antibiotic-resistant bacterial infections may be acquired and subsequently dispersed. The low overall detection of antibiotic-resistant E. coli in migratory birds sampled at remote sites in Alaska is consistent with the premise that anthropogenic inputs into the local environment or the relative lack thereof influences the prevalence of antibiotic-resistant bacteria among birds inhabiting the area.
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| 8. |
- van Dijk, Jacintha G. B., et al.
(författare)
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A Comparative Study of the Innate Humoral Immune Response to Avian Influenza Virus in Wild and Domestic Mallards
- 2020
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 11, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Domestic mallards (Anas platyrhynchos domesticus) are traditionally used as a model to investigate infection dynamics and immune responses to low pathogenic avian influenza viruses (LPAIVs) in free-living mallards. However, it is unclear whether the immune response of domestic birds reflects the response of their free-living counterparts naturally exposed to these viruses. We investigated the extent to which the innate humoral immune response was similar among (i) wild-type domestic mallards in primary and secondary infection with LPAIV H4N6 in a laboratory setting (laboratory mallards), (ii) wild-type domestic mallards naturally exposed to LPAIVs in a semi-natural setting (sentinel mallards), and (iii) free-living mallards naturally exposed to LPAIVs. We quantified innate humoral immune function by measuring non-specific natural antibodies (agglutination), complement activity (lysis), and the acute phase protein haptoglobin. We demonstrate that complement activity in the first 3 days after LPAIV exposure was higher in primary-exposed laboratory mallards than in sentinel and free-living mallards. LPAIV H4N6 likely activated the complement system and the acute phase response in primary-exposed laboratory mallards, as lysis was higher and haptoglobin lower at day 3 and 7 post-exposure compared to baseline immune function measured prior to exposure. There were no differences observed in natural antibody and haptoglobin concentrations among laboratory, sentinel, and free-living mallards in the first 3 days after LPAIV exposure. Our study demonstrates that, based on the three innate humoral immune parameters measured, domestic mallards seem an appropriate model to investigate innate immunology of their free-living counterparts, albeit the innate immune response of secondary-LPAIV exposed mallards is a better proxy for the innate immune response in pre-exposed free-living mallards than that of immunologically naive mallards.
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| 9. |
- Akaberi, Dario, 1989-
(författare)
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Identification of protease inhibitors against Flaviviruses and Coronaviruses
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vector-borne flaviviruses and coronaviruses of zoonotic origins are important human pathogens and represent a serious threat to public health worldwide. Flaviviruses can be found on all continents, apart from Antarctica, where they are transmitted by arthropod vectors causing millions of infections every year. While most of the infections are mild or asymptomatic, flaviviruses like dengue and yellow fever viruses can cause potentially lethal hemorrhagic fever and shock syndrome. Neurotropic flaviviruses like West Nile, Japanese encephalitis, and Tick-borne encephalitis (TBEV) can cause meningoencephalitis with long-term symptoms. Coronaviruses, and in particular betacoronaviruses of zoonotic origin like SARS (2003) and MERS (2012), have been periodically emerging since the early 2000s causing outbreaks of severe respiratory syndrome. The latest example is SARS-CoV-2 that after causing a cluster of infection in the Chinese city of Wuhan, spread all over the world causing at present over 6.9 million deaths. Although vaccines are essential in preventing infections or severe disease and hospitalization in the case of SARS-CoV-2, antivirals represent an extremely valuable tool for treatment and prevention of current and future flavivirus and coronavirus infections. In the work presented in this thesis we have used a combination of in silico and in vitro techniques to identify and test the activity of potential inhibitors of viral proteases. In our first study (paper 1) we unexpectedly identified an HIV protease inhibitor with in vitro activity against ZIKV NS2B-NS3 protease. The inhibitor was identified by virtual screening of a library of known protease inhibitors, evaluated by molecular dynamics simulation and finally tested against recombinant ZIKV protease using a FRET-based enzymatic assay. The same combination of molecular docking and molecular dynamics simulations were also used to correctly predict the activity of a known pan-Flavivirus protease inhibitor against TBEV protease (paper 2). As a result, we were the first to report peptide-based compounds with in vitro activity against TBEV. After the outbreak of the COVID-19 we switched our attention to SARS-CoV-2. We first tested the inhibitory effect of the broad-spectrum antiviral nitric oxide (NO) and found that the NO-releasing compound SNAP had a dose dependent inhibitory effect on SARS-CoV-2 replication in cell-based assays (paper 3). We speculated that SNAP could inhibit SARS-COV-2 protease by trans-nitration of the catalytic Cys145 of SARS-CoV-2 main protease and found that SNAP had a dose dependent inhibitory effect on recombinant SARS-CoV-2 Mpro protease activity in an in vitro enzymatic assay. In our last study (paper 4) we identified a new class of potent SARS-CoV-2 protease inhibitors through the affinity screening of DNA-encoded-chemical libraries containing 4.2 billion compounds. The identified compounds inhibited recombinant SARS-CoV-2 protease with IC50 as low as 25 nM and had a dose dependent antiviral effect in the low micromolar range in infected Calu-3 and Caco-2 cell lines.
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| 10. |
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