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Eriksson, P., Lindskog, C., Lorente-Leal, V., Waldenström, J., González-Acuna, D., Järhult, J. D., . . . Ellström, P. (2019). Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species: Support for the Community Concept. Frontiers in Microbiology, 10, Article ID 815.
Open this publication in new window or tab >>Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species: Support for the Community Concept
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2019 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 815Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
virus histochemistry, lectin staining, pattern of virus attachment, avian influenza, birds
National Category
Microbiology
Identifiers
urn:nbn:se:uu:diva-382841 (URN)10.3389/fmicb.2019.00815 (DOI)000464963200002 ()31057520 (PubMedID)
Funder
Swedish Research Council, 2015-03877Swedish Research Council, 2016-02596Knut and Alice Wallenberg Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2019-05-22 Created: 2019-05-22 Last updated: 2019-10-24Bibliographically approved
Levanov, L., Iheozor-Ejiofor, R. P., Lundkvist, Å., Vapalahti, O. & Plyusnin, A. (2019). Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis. Journal of General Virology, 100(2), 145-155
Open this publication in new window or tab >>Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis
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2019 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 100, no 2, p. 145-155Article in journal (Refereed) Published
Abstract [en]

Earlier four monoclonal antibodies (MAbs) against surface glycoproteins Gn and Gc of puumala virus (PUUV, genus Orthohantavirus, family Hantaviridae, order Bunyavirales) were generated and for three MAbs with neutralizing capacity the localization of binding epitopes was predicted using pepscan and phage-display techniques. In this work, we produced vesicular stomatitis virus (VSV) particles pseudotyped with the Gn and Gc glycoproteins of PUUV and applied site-directed mutagenesis to dissect the structure of neutralizing epitopes. Replacement of cysteine amino acid (aa) residues with alanines resulted in pseudotype particles with diminished (16 to 18 %) neut-titres; double Cys -> Ala mutants, as well as mutants with bulky aromatic and charged residues replaced with alanines, have shown even stronger reduction in neut-titres (from 25 % to the escape phenotype). In silico modelling of the neut-epitopes supported the hypothesis that these critical residues are located on the surface of viral glycoprotein molecules and thus can be recognized by the antibodies indeed. A similar pattern was observed in experiments with mutant pseudotypes and sera collected from patients suggesting that these neut-epitopes are utilized in a course of human PUUV infection. These data will help understanding the mechanisms of hantavirus neutralization and assist construction of vaccine candidates.

Place, publisher, year, edition, pages
MICROBIOLOGY SOC, 2019
Keywords
Monoclonal antibody, neutralizing epitope, site-directed mutagenesis
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-377671 (URN)10.1099/jgv.0.001202 (DOI)000457868300005 ()30624178 (PubMedID)
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Strand, T. M., Pineda, S., Backhans, A., Jakobsen, F., Råsbäck, T., Lõhmus, M., . . . Lundkvist, Å. (2019). Detection of Leptospira in Urban Swedish Rats: Pest Control Interventions as a Promising Source of Rats Used for Surveillance. Vector Borne and Zoonotic Diseases, 19(6), 414-420
Open this publication in new window or tab >>Detection of Leptospira in Urban Swedish Rats: Pest Control Interventions as a Promising Source of Rats Used for Surveillance
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2019 (English)In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 19, no 6, p. 414-420Article in journal (Refereed) Published
Abstract [en]

Rat carcasses obtained from pest control interventions can potentially be used for an efficient surveillance of zoonotic diseases such as leptospirosis. To evaluate the performance of different laboratory methods for detection of pathogenic Leptospira spp., heart and kidney samples from wild Norway rats were analyzed by microscopic agglutination test (MAT, the gold standard), a commercial IgG enzyme-linked immunosorbent assay, and by an optimized quantitative PCR (secY qPCR, followed by sequencing). We found secY qPCR to be as sensitive as MAT for screening of Leptospira infection in pest control rats and selected secY qPCR for a larger screening of rats from urban and rural areas in central and southern Sweden. We identified secY qPCR positive rats from the cities Stockholm, Gothenburg, and Malmö, which were further confirmed by sequencing.

Keywords
Norway rat, microscopic agglutination test, qPCR, zoonosis, Leptospira
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-388728 (URN)10.1089/vbz.2017.2262 (DOI)000474303200005 ()30785372 (PubMedID)
Funder
Swedish Research Council, 2017-05807
Available from: 2019-07-03 Created: 2019-07-03 Last updated: 2019-09-09Bibliographically approved
Ling, J., Verner-Carlsson, J., Eriksson, P., Plyusnina, A., Löhmus, M., Järhult, J. D., . . . Sironen, T. (2019). Genetic analyses of Seoul hantavirus genome recovered from rats (Rattus norvegicus) in the Netherlands unveils diverse routes of spread into Europe. Journal of Medical Virology, 91(5), 724-730
Open this publication in new window or tab >>Genetic analyses of Seoul hantavirus genome recovered from rats (Rattus norvegicus) in the Netherlands unveils diverse routes of spread into Europe
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2019 (English)In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 91, no 5, p. 724-730Article in journal (Refereed) Published
Abstract [en]

Seoul virus (SEOV) is the etiologic agent of hemorrhagic fever with renal syndrome. It is carried by brown rats (Rattus norvegicus), a commensal rodent that closely cohabitates with humans in urban environments. SEOV has a worldwide distribution, and in Europe, it has been found in rats in UK, France, Sweden, and Belgium, and human cases of SEOV infection have been reported in Germany, UK, France, and Belgium. In the search of hantaviruses in brown rats from the Netherlands, we found both serological and genetic evidence for the presence of SEOV in the local wild rat population. To further decipher the relationship with other SEOV variants globally, the complete genome of SEOV in the Netherlands was recovered. SEOV sequences obtained from three positive rats (captured at close trapping locations at the same time) were found highly similar. Phylogenetic analyses demonstrated that two lineages of SEOV circulate in Europe. Strains from the Netherlands and UK, together with the Baxter strain from US, constitute one of these two, while the second includes strains from Europe and Asia. Our results support a hypothesis of diverse routes of SEOV spread into Europe. These findings, combined with other indications on the expansion of the spatial European range of SEOV, suggest an increased risk of this virus for the public health, highlighting the need for increased surveillance.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
hantavirus, hemorrhagic fever with renal syndrome, phylogenetic analysis, Seoul virus
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-379878 (URN)10.1002/jmv.25390 (DOI)000460471800002 ()30609070 (PubMedID)
Funder
Swedish Research Council, 2017-05807
Available from: 2019-03-27 Created: 2019-03-27 Last updated: 2019-03-27Bibliographically approved
Ling, J., Smura, T., Lundström, J. O., Pettersson, J., Sironen, T., Vapalahti, O., . . . Hesson, J. C. (2019). Introduction and Dispersal of Sindbis Virus from Central Africa to Europe. Journal of Virology, 93(16), Article ID e00620-19.
Open this publication in new window or tab >>Introduction and Dispersal of Sindbis Virus from Central Africa to Europe
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2019 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 93, no 16, article id e00620-19Article in journal (Refereed) Published
Abstract [en]

Bird-hosted viruses have the potential to be transported over large areas of the world and to be transmitted in distant geographical regions. Sindbis virus (SINV) is a mosquito-borne alphavirus that is locally amplified in a bird-mosquito enzootic cycle and distributed all over the Old World and Australia/Oceania. Sindbis virus genotype I (SINV-I) is the cause of disease outbreaks in humans in South Africa as well as in northern Europe. To trace the evolutionary history and potential strain-disease association of SINV-I, we sequenced 36 complete genomes isolated from field material in Europe, as well as in Africa and the Middle East, collected over 58 years. These were analyzed together with 30 additional published whole SINV-I genomes using Bayesian analysis. Our results suggested that SINV-I was introduced only once to northern Europe from central Africa, in the 1920s. After its first introduction to Sweden, it spread east and southward on two separate occasions in the 1960s and 1970s. Another introduction from central Africa to southern/central Europe seems to have occurred, and where these two introductions meet, one recombination event was detected in central Europe. In addition, another recombinant strain was found in central Africa, where the most divergent SINV-I strains also originated. IMPORTANCE This study shows that only a single introduction of SINV into a new geographical area is required for spread and establishment, provided that the requisite vector(s) and reservoir(s) of epizootological and epidemiological importance are present. Furthermore, we present the first report of recombination between two strains of SINV in nature. Our study increases the knowledge on new introductions and dispersal of arboviruses in general and of SINV in particular.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY, 2019
Keywords
evolution, phylogeny, Sindbis virus
National Category
Zoology
Identifiers
urn:nbn:se:uu:diva-393619 (URN)10.1128/JVI.00620-19 (DOI)000480711400020 ()31142666 (PubMedID)
Funder
Swedish Research Council, 2017-05807Swedish Research Council Formas, 2015-710
Available from: 2019-09-26 Created: 2019-09-26 Last updated: 2019-09-26Bibliographically approved
Lundström, J. O., Hesson, J. C., Schafer, M. L., Ostman, O., Semmler, T., Bekaert, M., . . . Pfeffer, M. (2019). Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors. PLoS Neglected Tropical Diseases, 13(8), Article ID e0007702.
Open this publication in new window or tab >>Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors
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2019 (English)In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 13, no 8, article id e0007702Article in journal (Refereed) Published
Abstract [en]

Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalalven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalalven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-396550 (URN)10.1371/journal.pntd.0007702 (DOI)000490919400075 ()31465453 (PubMedID)
Available from: 2019-11-07 Created: 2019-11-07 Last updated: 2019-11-07Bibliographically approved
Hoffman, T., Lindeborg, M., Barboutis, C., Erciyas-Yavuz, K., Evander, M., Fransson, T., . . . Salaneck, E. (2018). Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor. Emerging Infectious Diseases, 24(5), 879-882
Open this publication in new window or tab >>Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor
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2018 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 5, p. 879-882Article in journal (Refereed) Published
Abstract [en]

Alkhurma hemorrhagic fever virus RNA was detected in immature Hyalomma rufipes ticks infesting northward migratory birds caught in the North Mediterranean Basin. This finding suggests a role for birds in the ecology of the Alkhurma hemorrhagic fever virus and a potential mechanism for dissemination to novel regions. Increased surveillance is warranted.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-354104 (URN)10.3201/eid2405.171369 (DOI)000430355500010 ()29664386 (PubMedID)
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-12-18Bibliographically approved
Wille, M., Bröjer, C., Lundkvist, Å. & Järhult, J. D. (2018). Alternate routes of influenza A virus infection in Mallard (Anas platyrhynchos). Veterinary research (Print), 49, Article ID 110.
Open this publication in new window or tab >>Alternate routes of influenza A virus infection in Mallard (Anas platyrhynchos)
2018 (English)In: Veterinary research (Print), ISSN 0928-4249, E-ISSN 1297-9716, Vol. 49, article id 110Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-369685 (URN)10.1186/s13567-018-0604-0 (DOI)000448861600003 ()
Available from: 2018-12-16 Created: 2018-12-16 Last updated: 2018-12-18Bibliographically approved
Strand, T., Lundkvist, Å., Olsen, B. & Gustafsson, L. (2018). Breeding consequences of flavivirus infection in the collared flycatcher. BMC Evolutionary Biology, 18, Article ID 13.
Open this publication in new window or tab >>Breeding consequences of flavivirus infection in the collared flycatcher
2018 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 18, article id 13Article in journal (Refereed) Published
Abstract [en]

Background: The breeding consequences of virus infections have rarely been studied in avian natural breeding populations. In this paper we investigated the links between humoral immunity following a natural flavivirus infection and reproduction in a wild bird population of collared flycatcher (Ficedula albicollis). We analyzed plasma from 744 birds for antibodies and correlated these results to a number of reproductive components.

Results: Nearly one third (27.8%) of the sampled collared flycatchers were found seropositive for flavivirus. Males had significantly more frequently flavivirus antibodies (32.3%) than females (25.1%). Seropositive females differed significantly from seronegative females in four traits: they had earlier lay date, higher body weight, higher survival rate and were older than seronegative females. The females did not differ in clutch size, number of fledged young or number of recruited young. Seropositive males had female partners with earlier lay date, i.e. the males bred earlier and they also produced more fledged young than seronegative males. In contrast, the males did not differ in clutch size, number of recruited young, male weight, age or survival. Interestingly, seropositive males had larger ornament, forehead badge size, than seronegative males.

Conclusions: Collared flycatchers with an antibody response against flavivirus were more successful than birds with no antibody response, for any of the measured life history traits. The positive link between flavivirus antibody presence and life-history trait levels suggest that it is condition dependent in the collared flycatcher.

National Category
Natural Sciences
Research subject
Biology with specialization in Animal Ecology
Identifiers
urn:nbn:se:uu:diva-344684 (URN)10.1186/s12862-018-1121-5 (DOI)000424461700001 ()29402209 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research Council
Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-28Bibliographically approved
Eriksson, P., Lindskog, C., Engholm, E., Blixt, O., Waldenstrom, J., Munster, V., . . . Ellstrom, P. (2018). Characterization of avian influenza virus attachment patterns to human and pig tissues. Scientific Reports, 8, Article ID 12215.
Open this publication in new window or tab >>Characterization of avian influenza virus attachment patterns to human and pig tissues
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12215Article in journal (Refereed) Published
Abstract [en]

Wild birds of Anseriformes and Charadriiformes are natural reservoirs of influenza A viruses (IAVs). Occasionally, IAVs transmit and adapt to mammalian hosts, and are maintained as epidemic strains in their new hosts. Viral adaptions to mammalian hosts include altered receptor preference of host epithelial sialylated oligosaccharides from terminal alpha 2,3-linked sialic acid (SA) towards alpha 2,6-linked SA. However, alpha 2,3-linked SA has been found in human respiratory tract epithelium, and human infections by avian IAVs (AIVs) have been reported. To further explore the attachment properties of AIVs, four AIVs of different subtypes were investigated on human and pig tissues using virus histochemistry. Additionally, glycan array analysis was performed for further characterization of IAVs' receptor structure tropism. Generally, AIV attachment was more abundant to human tissues than to pig tissues. The attachment pattern was very strong to human conjunctiva and upper respiratory tract, but variable to the lower respiratory tract. AIVs mainly attached to alpha 2,3-linked SA, but also to combinations of alpha 2,3-and alpha 2,6-linked SA. The low attachment of these AIV isolates to pig tissues, but high attachment to human tissues, addresses the question whether AIVs in general require passage through pigs to obtain adaptions towards mammalian receptor structures.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Microbiology
Identifiers
urn:nbn:se:uu:diva-362683 (URN)10.1038/s41598-018-29578-1 (DOI)000441625500038 ()30111851 (PubMedID)
Funder
Swedish Research Council, 2015-03877Swedish Research Council, 2016-02596Knut and Alice Wallenberg Foundation
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2019-10-24Bibliographically approved
Projects
Occurrence and fate of the antiviral drug Oseltamivir in aquatic environments and the effect on resistance development in influenza A viruses [2008-1239_Formas]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8608-6551

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