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Latorre-Margalef, Neus
Publications (10 of 27) Show all publications
Wille, M., Latorre-Margalef, N., Tolf, C., Halpin, R., Wentworth, D., Fouchier, R. A. M., . . . Waldenström, J. (2018). Where do all the subtypes go?: Temporal dynamics of H8-H12 influenza A viruses in waterfowl. Virus Evolution, 4(2), Article ID vey025.
Open this publication in new window or tab >>Where do all the subtypes go?: Temporal dynamics of H8-H12 influenza A viruses in waterfowl
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2018 (English)In: Virus Evolution, E-ISSN 2057-1577, Vol. 4, no 2, article id vey025Article in journal (Refereed) Published
Abstract [en]

Influenza A virus (IAV) is ubiquitous in waterfowl. In the northern hemisphere IAV prevalence is highest during the autumn and coincides with a peak in viral subtype diversity. Although haemagglutinin subtypes H1-H12 are associated with waterfowl hosts, subtypes H8-H12 are detected very infrequently. To better understand the role of waterfowl in the maintenance of these rare subtypes, we sequenced H8-H12 viruses isolated from Mallards (Anas platyrhynchos) from 2002 to 2009. These rare viruses exhibited varying ecological and phylodynamic features. The Eurasian clades of H8 and H12 phylogenies were dominated by waterfowl sequences; mostly viruses sequenced in this study. H11, once believed to be a subtype that infected charadriiformes (shorebirds), exhibited patterns more typical of common virus subtypes. Finally, subtypes H9 and H10, which have maintained lineages in poultry, showed markedly different patterns: H10 was associated with all possible NA subtypes and this drove HA lineage diversity within years. Rare viruses belonging to subtypes H8-H12 were highly reassorted, indicating that these rare subtypes are part of the broader IAV pool. Our results suggest that waterfowl play a role in the maintenance of these rare subtypes, but we recommend additional sampling of non-traditional hosts to better understand the reservoirs of these rare viruses.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
disease ecology, evolutionary genetics, influenza A, mallards, pathogen dynamics, subtype diversity
National Category
Microbiology
Research subject
Biomedical Sciences, Virology; Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-80290 (URN)10.1093/ve/vey025 (DOI)000456426800007 ()30151242 (PubMedID)
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved
Nykvist, M., Gillman, A., Söderström Lindström, H., Tang, C., Fedorova, G., Lundkvist, Å., . . . Järhult, J. D. (2017). In vivo mallard experiments indicate that zanamivir has less potential for environmental influenza A virus resistance development than oseltamivir. Journal of General Virology, 98(12), 2937-2949
Open this publication in new window or tab >>In vivo mallard experiments indicate that zanamivir has less potential for environmental influenza A virus resistance development than oseltamivir
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2017 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 98, no 12, p. 2937-2949Article in journal (Refereed) Published
Abstract [en]

Neuraminidase inhibitors are a cornerstone of influenza pandemic preparedness before vaccines can be mass-produced and thus a neuraminidase inhibitor-resistant pandemic is a serious threat to public health. Earlier work has demonstrated the potential for development and persistence of oseltamivir resistance in influenza A viruses exposed to environmentally relevant water concentrations of the drug when infecting mallards, the natural influenza reservoir that serves as the genetic base for human pandemics. As zanamivir is the major second-line neuraminidase inhibitor treatment, this study aimed to assess the potential for development and persistence of zanamivir resistance in an in vivo mallard model; especially important as zanamivir will probably be increasingly used. Our results indicate less potential for development and persistence of resistance due to zanamivir than oseltamivir in an environmental setting. This conclusion is based on: (1) the lower increase in zanamivir IC50 conferred by the mutations caused by zanamivir exposure (2–17-fold); (2) the higher zanamivir water concentration needed to induce resistance (at least 10 µg l−1); (3) the lack of zanamivir resistance persistence without drug pressure; and (4) the multiple resistance-related substitutions seen during zanamivir exposure (V116A, A138V, R152K, T157I and D199G) suggesting lack of one straight-forward evolutionary path to resistance. Our study also adds further evidence regarding the stability of the oseltamivir-induced substitution H275Y without drug pressure, and demonstrates the ability of a H275Y-carrying virus to acquire secondary mutations, further boosting oseltamivir resistance when exposed to zanamivir. Similar studies using influenza A viruses of the N2-phylogenetic group of neuraminidases are recommended.

Place, publisher, year, edition, pages
Society for General Microbiology, 2017
National Category
Microbiology
Research subject
Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-74136 (URN)10.1099/jgv.0.000977 (DOI)000417312300007 ()29139346 (PubMedID)2-s2.0-85037721670 (Scopus ID)
Funder
Swedish Research Council, 2016-02606Swedish Research Council Formas, 211-2013-1320;2016-00790
Available from: 2018-05-09 Created: 2018-05-09 Last updated: 2019-08-29Bibliographically approved
Wille, M., Latorre-Margalef, N., Tolf, C., Stallknecht, D. E. & Waldenström, J. (2017). No evidence for homosubtypic immunity of influenza H3 in Mallards following vaccination in a natural experimental system. Molecular Ecology, 26(5), 1420-1431
Open this publication in new window or tab >>No evidence for homosubtypic immunity of influenza H3 in Mallards following vaccination in a natural experimental system
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2017 (English)In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 26, no 5, p. 1420-1431Article in journal (Refereed) Published
Abstract [en]

The Mallard (Anas platyrhynchos) is an important reservoir species for influenza A viruses (IAV), and in this host, prevalence and virus diversity are high. Studies have demonstrated the presence of homosubtypic immunity, where individuals are unlikely to be reinfected with the same subtype within an autumn season. Further, evidence for heterosubtypic immunity exists, whereby immune responses specific for one subtype offer partial or complete protection against related HA subtypes. We utilized a natural experimental system to determine whether homo- or heterospecific immunity could be induced following experimental vaccination. Thirty Mallards were vaccinated with an inactivated H3, H6 or a sham vaccine and after seroconversion were exposed to naturally infected wild conspecifics. All ducks were infected within 2days and had both primary and secondary infections. Overall, there was no observable difference between groups; all individuals were infected with H3 and H10 IAV. At the cessation of the experiment, most individuals had anti-NP antibodies and neutralizing antibodies against H10. Not all individuals had H3 neutralizing antibodies. The isolated H3 IAVs revealed genetic dissimilarity to the H3 vaccine strain, specifically substitutions in the vicinity of the receptor-binding site. There was no evidence of vaccine-induced homosubtypic immunity to H3, a likely result of both a poor H3 immune response in the ducks and H3 immune escape. Likewise, there was no observed heterosubtypic protection related to H6 vaccination. This study highlights the need for experimental approaches to assess how exposure to pathogens and resulting immune processes translates to individual and population disease dynamics.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2017
Keywords
Anas platyrhynchos, H3, homosubtypic immunity, humoral immunity, immunity, influenza A virus, Mallard
National Category
Ecology Microbiology
Research subject
Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-64211 (URN)10.1111/mec.13967 (DOI)000395700600015 ()27997047 (PubMedID)2-s2.0-85013040569 (Scopus ID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2019-08-29Bibliographically approved
Avril, A., Grosbois, V., Latorre-Margalef, N., Gaidet, N., Tolf, C., Olsen, B. & Waldenström, J. (2016). Capturing individual-level parameters of influenza A virus dynamics in wild ducks using multistate models. Journal of Applied Ecology, 53(4), 1289-1297
Open this publication in new window or tab >>Capturing individual-level parameters of influenza A virus dynamics in wild ducks using multistate models
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2016 (English)In: Journal of Applied Ecology, ISSN 0021-8901, E-ISSN 1365-2664, Vol. 53, no 4, p. 1289-1297Article in journal (Refereed) Published
Abstract [en]

Disease prevalence in wildlife is governed by epidemiological parameters (infection and recovery rates) and response to infection, both of which vary within and among individual hosts. Studies quantifying these individual-scale parameters and documenting their source of variation in wild hosts are fundamental for predicting disease dynamics. Such studies do not exist for the influenza A virus (IAV), despite its strong impact on the global economy and public health. Using capture-recaptures of 3500 individual mallards Anas platyrhynchos during seven migration seasons at a stopover site in southern Sweden, we provide the first empirical description of the individual-based mechanisms of IAV dynamics in a wild reservoir host. For most years, prevalence and risk of IAV infection peaked at a single time during the autumn migration season, but the timing, shape and intensity of the infection curve showed strong annual heterogeneity. In contrast, the seasonal pattern of recovery rate only varied in intensity across years. Adults and juveniles displayed similar seasonal patterns of infection and recovery each year. However, compared to adults, juveniles experienced twice the risk of becoming infected, whereas recovery rates were similar across age categories. Finally, we did not find evidence that infection influenced the timing of emigration.Synthesis and applications. Our study provides robust empirical estimates of epidemiological parameters for predicting influenza A virus (IAV) dynamics. However, the strong annual variation in infection curves makes forecasting difficult. Prevalence data can provide reliable surveillance indicators as long as they catch the variation in infection risk. However, individual-based monitoring of infection is required to verify this assumption in areas where surveillance occurs. In this context, monitoring of captive sentinel birds kept in close contact with wild birds is useful. The fact that infection does not impact the timing of migration underpins the potential for mallards to spread viruses rapidly over large geographical scales. Hence, we strongly encourage IAV surveillance with a multistate capture-recapture approach along the entire migratory flyway of mallards.

Keywords
avian influenza, epidemiology, host-pathogen dynamics, individual-based monitoring, influenza A virus, multistate capture-recapture, outbreaks, SIR model, waterfowl, zoonosis
National Category
Ecology
Research subject
Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-55770 (URN)10.1111/1365-2664.12699 (DOI)000380065600033 ()2-s2.0-84973607340 (Scopus ID)
Available from: 2016-08-26 Created: 2016-08-26 Last updated: 2018-10-24Bibliographically approved
Latorre-Margalef, N., Avril, A., Tolf, C., Olsen, B. & Waldenström, J. (2016). How Does Sampling Methodology Influence Molecular Detection and Isolation Success in Influenza A Virus Field Studies?. Applied and Environmental Microbiology, 82(4), 1147-1153
Open this publication in new window or tab >>How Does Sampling Methodology Influence Molecular Detection and Isolation Success in Influenza A Virus Field Studies?
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2016 (English)In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 82, no 4, p. 1147-1153Article in journal (Refereed) Published
Abstract [en]

Wild waterfowl are important reservoir hosts for influenza A virus (IAV) and a potential source of spillover infections in other hosts, including poultry and swine. The emergence of highly pathogenic avian influenza (HPAI) viruses, such as H5N1 and H5N8, and subsequent spread along migratory flyways prompted the initiation of several programs in Europe, North America, and Africa to monitor circulation of HPAI and low-pathogenicity precursor viruses (low-pathogenicity avian influenza [LPAI] viruses). Given the costs of maintaining such programs, it is essential to establish best practice for field methodologies to provide robust data for epidemiological interpretation. Here, we use long-term surveillance data from a single site to evaluate the influence of a number of parameters on virus detection and isolation of LPAI viruses. A total of 26,586 samples (oropharyngeal, fecal, and cloacal) collected from wild mallards were screened by real-time PCR, and positive samples were subjected to isolation in embryonated chicken eggs. The LPAI virus detection rate was influenced by the sample type: cloacal/fecal samples showed a consistently higher detection rate and lower cycle threshold (Ct) value than oropharyngeal samples. Molecular detection was more sensitive than isolation, and virus isolation success was proportional to the number of RNA copies in the sample. Interestingly, for a given Ct value, the isolation success was lower in samples from adult birds than in those from juveniles. Comparing the results of specific real-time reverse transcriptase (RRT)-PCRs and of isolation, it was clear that coinfections were common in the investigated birds. The effects of sample type and detection methods warrant some caution in interpretation of the surveillance data.

National Category
Microbiology
Research subject
Natural Science, Microbiology; Natural Science, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-49927 (URN)10.1128/AEM.03283-15 (DOI)000369375900017 ()2-s2.0-84957916893 (Scopus ID)
Available from: 2016-02-26 Created: 2016-02-26 Last updated: 2017-11-30Bibliographically approved
Lewis, N. S., Verhagen, J. H., Javakhishvili, Z., Russell, C. A., Lexmond, P., Westgeest, K. B., . . . de Graaf, M. (2015). Influenza A virus evolution and spatio-temporal dynamics in Eurasian wild birds: a phylogenetic and phylogeographical study of whole-genome sequence data. Journal of General Virology, 96, 2050-2060
Open this publication in new window or tab >>Influenza A virus evolution and spatio-temporal dynamics in Eurasian wild birds: a phylogenetic and phylogeographical study of whole-genome sequence data
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2015 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 96, p. 2050-2060Article in journal (Refereed) Published
Abstract [en]

Low pathogenic avian influenza A viruses (IAVs) have a natural host reservoir in wild waterbirds and the potential to spread to other host species. Here, we investigated the evolutionary, spatial and temporal dynamics of avian IAVs in Eurasian wild birds. We used whole-genome sequences collected as part of an intensive long-term Eurasian wild bird surveillance study, and combined this genetic data with temporal and spatial information to explore the virus evolutionary dynamics. Frequent reassortment and co-circulating lineages were observed for all eight genomic RNA segments over time. There was no apparent species-specific effect on the diversity of the avian IAVs. There was a spatial and temporal relationship between the Eurasian sequences and significant viral migration of avian lAVs from West Eurasia towards Central Eurasia. The observed viral migration patterns differed between segments. Furthermore, we discuss the challenges faced when analysing these surveillance and sequence data, and the caveats to be borne in mind when drawing conclusions from the apparent results of such analyses.

National Category
Microbiology
Research subject
Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-46907 (URN)10.1099/vir.0.000155 (DOI)000362243000007 ()25904147 (PubMedID)2-s2.0-84938127397 (Scopus ID)
Available from: 2015-10-26 Created: 2015-10-26 Last updated: 2020-01-28Bibliographically approved
Gillman, A., Muradrasoli, S., Söderström, H., Holmberg, F., Latorre-Margalef, N., Tolf, C., . . . Jarhult, J. D. (2015). Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards. Applied and Environmental Microbiology, 81(7), 2378-2383
Open this publication in new window or tab >>Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
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2015 (English)In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 81, no 7, p. 2378-2383Article in journal (Refereed) Published
Abstract [en]

Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.

National Category
Biological Sciences
Research subject
Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-42828 (URN)10.1128/AEM.04034-14 (DOI)000351842000013 ()25616792 (PubMedID)2-s2.0-84925379512 (Scopus ID)
Available from: 2015-04-23 Created: 2015-04-23 Last updated: 2020-01-28Bibliographically approved
Latorre-Margalef, N., Tolf, C., Grosbois, V., Avril, A., Bengtsson, D., Wille, M., . . . Waldenström, J. (2014). Long-term variation in influenza A virus prevalence and subtype diversity in migratory mallards in northern Europe.. Proceedings of the Royal Society of London. Biological Sciences, 281(1781), Article ID: UNSP 20140098
Open this publication in new window or tab >>Long-term variation in influenza A virus prevalence and subtype diversity in migratory mallards in northern Europe.
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2014 (English)In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 281, no 1781, p. Article ID: UNSP 20140098-Article in journal (Refereed) Published
Abstract [en]

Data on long-term circulation of pathogens in wildlife populations are seldom collected, and hence understanding of spatial-temporal variation in prevalence and genotypes is limited. Here, we analysed a long-term surveillance series on influenza A virus (IAV) in mallards collected at an important migratory stopover site from 2002 to 2010, and characterized seasonal dynamics in virus prevalence and subtype diversity. Prevalence dynamics were influenced by year, but retained a common pattern for all years whereby prevalence was low in spring and summer, but increased in early autumn with a first peak in August, and a second more pronounced peak during October-November. A total of 74 haemagglutinin (HA)/neuraminidase (NA) combinations were isolated, including all NA and most HA (H1-H12) subtypes. The most common subtype combinations were H4N6, H1N1, H2N3, H5N2, H6N2 and H11N9, and showed a clear linkage between specific HA and NA subtypes. Furthermore, there was a temporal structuring of subtypes within seasons based on HA phylogenetic relatedness. Dissimilar HA subtypes tended to have different temporal occurrence within seasons, where the subtypes that dominated in early autumn were rare in late autumn, and vice versa. This suggests that build-up of herd immunity affected IAV dynamics in this system.

National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-33714 (URN)10.1098/rspb.2014.0098 (DOI)000332640400028 ()24573857 (PubMedID)2-s2.0-84896886284 (Scopus ID)
Available from: 2014-04-09 Created: 2014-04-09 Last updated: 2020-01-28Bibliographically approved
Olson, S. H., Parmley, J., Soos, C., Gilbert, M., Latorre-Margalef, N., Hall, J. S., . . . Joly, D. (2014). Sampling Strategies and Biodiversity of Influenza A Subtypes in Wild Birds. PLoS ONE, 9(3), Article ID e90826.
Open this publication in new window or tab >>Sampling Strategies and Biodiversity of Influenza A Subtypes in Wild Birds
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, article id e90826Article in journal (Refereed) Published
Abstract [en]

Wild aquatic birds are recognized as the natural reservoir of avian influenza A viruses (AIV), but across high and low pathogenic AIV strains, scientists have yet to rigorously identify most competent hosts for the various subtypes. We examined 11,870 GenBank records to provide a baseline inventory and insight into patterns of global AIV subtype diversity and richness. Further, we conducted an extensive literature review and communicated directly with scientists to accumulate data from 50 non-overlapping studies and over 250,000 birds to assess the status of historic sampling effort. We then built virus subtype sample-based accumulation curves to better estimate sample size targets that capture a specific percentage of virus subtype richness at seven sampling locations. Our study identifies a sampling methodology that will detect an estimated 75% of circulating virus subtypes from a targeted bird population and outlines future surveillance and research priorities that are needed to explore the influence of host and virus biodiversity on emergence and transmission.

National Category
Microbiology
Research subject
Ecology, Zoonotic Ecology
Identifiers
urn:nbn:se:lnu:diva-33850 (URN)10.1371/journal.pone.0090826 (DOI)000332479400137 ()2-s2.0-84897148224 (Scopus ID)
Available from: 2014-04-11 Created: 2014-04-11 Last updated: 2017-12-05Bibliographically approved
Wille, M., Tolf, C., Avril, A., Latorre-Margalef, N., Wallerström, S., Olsen, B. & Waldenström, J. (2013). Frequency and patterns of reassortment in natural influenza A virus infection in a reservoir host. Virology, 443(15), 150-160
Open this publication in new window or tab >>Frequency and patterns of reassortment in natural influenza A virus infection in a reservoir host
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2013 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 443, no 15, p. 150-160Article in journal (Refereed) Published
Abstract [en]

Influenza A viruses (IAV) can dramatically alter both genotype and phenotype at a rapid rate as a product of co-infection and reassortment Avian IAV exhibit high levels of phylogenetic incongruence, suggesting high levels of reassortment in the virus reservoir. Using a natural-experimental system, we reconstructed relationships amongst 92 viruses across 15 subtypes from 10 Mallards in an autumn season. Phylogenetic analyses estimated that 56% of the isolated viruses were reassorted. Network analysis demonstrated different patterns of reassortment and limited exchange of segments between primary and secondary infections. No clear patterns of linkage between segments were found, and patterns within a season were likely the consequence of continued introduction ofnew constellations, high viral load and diversity in the wild bird reservoir, and co-infections. This is the first IAV study to implement multiple tools available for elucidating factors governing reassortment patterns in naturally infected Mallards.

National Category
Microbiology
Research subject
Natural Science, Microbiology
Identifiers
urn:nbn:se:lnu:diva-32897 (URN)10.1016/j.virol.2013.05.004 (DOI)000322289900017 ()2-s2.0-84879784330 (Scopus ID)
Available from: 2014-03-17 Created: 2014-03-17 Last updated: 2020-01-28Bibliographically approved
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