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  • 101.
    Tjomsland, Veronica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Borendal Wodlin, Ninni
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lifson, Jeffrey
    SAIC/Fredrick, National Cancer Institute at Fredrick, Frederick, Maryland, USA.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions2013In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 43, no 9, p. 2361-2372Article in journal (Refereed)
    Abstract [en]

    The initial interaction between HIV-1 and the host occurs at the mucosa during sexual intercourse. In cervical mucosa, HIV-1 exists both as free and opsonized virions and this might influence initial infection. We used cervical explants to study HIV-1 transmission, the effects of opsonization on infectivity, and how infection can be prevented. Complement opsonization enhanced HIV-1 infection of dendritic cells (DCs) compared with that by free HIV-1, but this increased infection was not observed with CD4+ T cells. Blockage of the α4-, β7-, and β1-integrins significantly inhibited HIV-1 infection of both DCs and CD4+ T cells. We found a greater impairment of HIV-1 infection in DCs for complement-opsonized virions compared with that of free virions when αM/β2- and α4-integrins were blocked. Blocking the C-type lectin receptor macrophage mannose receptor (MMR) inhibited infection of emigrating DCs but had no effect on CD4+ T-cell infection. We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4+ T cells emigrating from the cervical tissues. These findings may provide the basis of novel microbicidal strategies that may help limit or prevent initial infection of the cervical mucosa, thereby reducing or averting systemic HIV-1 infection.

  • 102.
    Tjomsland, Veronica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Lifson, Jeffrey D
    AIDS and Cancer Virus Program, SAIC Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland, USA.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Blocking of integrins significantly inhibits HIV-1 infection of human cervical mucosa immune cells and development of founder populations2011Manuscript (preprint) (Other academic)
    Abstract [en]

    Slightly more than half of the HIV-1 infected individuals in the world are women and almost all acquire the infection through sexual intercourse. The initial interaction between HIV-1 and the host occurs at the mucosa site and the most common mode to access the submucosa is through dendritic cells (DCs). In the cervical mucosa, HIV-1 exist both as free and opsonized virions and this might influence initial infection. We used a cervical tissue explant model and both free and opsonized virions to study HIV-1 transmission and how it can be prevented.

    We found that complement opsonization significantly enhanced HIV-1 infection of DCs compared to free HIV-1, but this increased infection was not seen for CD4+ T cells. Blocking of α4, β7, and β1 integrins demonstrated significant inhibition of infection of both DCs and CD4+ T cells emigrating from mucosa, independent of the use of free or complement opsonized HIV-1. We found a higher impairment of HIV-1 infection in emigrating DCs for complement opsonized virions compared to free virions when the use of αM/β2 and α4 integrins was blocked.

    This study showed that block of integrins decreased the HIV-1 infection of both DCs and CD4+ T cells emigrating from the cervical explant tissues and, remarkably, the establishment of founder populations in these tissues. This indicates that preventing or severely lowering initial infection of the cervical mucosa could avert systemic HIV-1 infection and should be considered for development of microbicides to prevent HIV infection and transmission.

  • 103.
    Veldhuis Kroeze, Edwin J. B.
    et al.
    ViroClinics Biosciences BV, Rotterdam, The Netherlands.
    Stittelaar, Koert J.
    ViroClinics Biosciences BV, Rotterdam, The Netherlands.
    Teeuwsen, Vera J.
    ViroClinics Biosciences BV, Rotterdam, The Netherlands.
    Dijkshoorn, Marcel L
    Erasmus Medical Center, Rotterdam, The Netherlands.
    van Amerongen, Geert
    ViroClinics Biosciences BV, Rotterdam, The Netherlands.
    de Waal, Leon
    ViroClinics Biosciences BV, Rotterdam, The Netherlands.
    Kuiken, Thijs
    Erasmus Medical Center, Rotterdam, The Netherlands.
    Krestin, Gabriel P.
    Erasmus Medical Center, Rotterdam, The Netherlands.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Osterhaus, Albert D. M. E
    ViroClinics Biosciences BV, Rotterdam, The Netherlands.
    Consecutive CT in vivo lung imaging as quantitative parameter of influenza vaccine efficacy in the ferret model2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 51, p. 7391-7394Article in journal (Refereed)
    Abstract [en]

    Preclinical vaccine efficacy studies are generally limited to certain read out parameters such as assessment of virus titers in swabs and organs, clinical signs, serum antibody titers, and pathological changes. These parameters are not always routinely applied and not always scheduled in a logical standardized way. We used computed tomography (CT) imaging as additional and novel read out parameter in a vaccine efficacy study by quantifying alterations in aerated lung volumes in ferrets challenged with the 2009 pandemic A/H1N1 influenza virus.

    Vaccination protected from marked variations in aerated lung volumes compared to naive controls. The vaccinated group showed a daily gradual mean reduction with a maximum of 7.8%, whereas the controls showed a maximum of 14.3% reduction. The pulmonary opacities evident on CT images were most pronounced in the placebo-treated controls, and corresponded to significantly increased relative lung weights at necropsy.

    This study shows that consecutive in vivo CT imaging allows for a day to day read out of vaccine efficacy by quantification of altered aerated lung volumes. 

  • 104.
    Vilchez, Samuel
    et al.
    Karolinska University Hospital.
    Reyes, Daniel
    UNAN.
    Paniagua, Margarita
    UNAN.
    Bucardo, Filemon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Mollby, Roland
    Karolinska Institute.
    Weintraub , Andrej
    Karolinska University Hospital.
    Prevalence of diarrhoeagenic Escherichia coli in children from Leon, Nicaragua2009In: JOURNAL OF MEDICAL MICROBIOLOGY, ISSN 0022-2615 , Vol. 58, no 5, p. 630-637Article in journal (Refereed)
    Abstract [en]

    Diarrhoeal disease is a public health problem worldwide, mostly affecting children in developing countries. In Nicaragua, diarrhoea is the second greatest cause of infant mortality. During the period March 2005 to September 2006, a total of 526 faecal samples from children aged 0-60 months (381 with and 145 without diarrhoea) from Leon, Nicaragua, were studied. In order to detect five different diarrhoeagenic Escherichia coli pathotypes simultaneously [enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterohaemorrhagic E. coli (EHEC) and enteroinvasive E. coli (EIEC)], a mixture of eight primer pairs was used in a single PCR. At least one diarrhoeagenic E. coli pathotype was detected in 205 samples (53.8%) of the diarrhoea group and in 77 samples (53.1 %) in the non-diarrhoea group. ETEC was detected significantly more often in children with diarrhoea (20.5 %) than in children without diarrhoea (8.3%) (P=0.001). Atypical EPEC, EIEC and EAEC were detected with slightly lower frequencies in children with (16.0, 0.8 and 27.8%, respectively) than in children without (20.7, 1.4 and 33.1 %,respectively) diarrhoea. EHEC was only detected in children with diarrhoea (2.1%). In conclusion, ETEC continues to be an important agent associated with diarrhoea in children from Leon, Nicaragua. Although not very frequent, the only findings that were 100 % associated with diarrhoea were ETEC estA (4.7%) and EH EC (2.1%). Nevertheless, EAEC and EPEC were also frequent pathotypes in the population under study. In children with severe diarrhoea, more than half had EAEC, ETEC or EPEC, and EAEC was the most prevalent pathotype.

  • 105.
    Vildevall, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    The Norovirus Puzzle: Characterization of human and bovine norovirus susceptibility patterns2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Winter vomiting disease is caused by norovirus (NoV) and affects millions of people every year resulting in 200.000 deaths among children in developing countries. It was observed early that not all individuals exposed to the norovirus became ill. The reason for this is now recognized to be dependent upon the secretor status of an individual. The secretor status determines the ability of an individual to express histo-blood group antigens (HBGA) on mucosa and in saliva. A non-secretor is unable to express HBGAs due to a mutation in a gene called FUT2. In this thesis, I have investigated the antibody prevalence and titer in humans in Sweden and Nicaragua to the most common GII NoV and the correlation to secretor status, Lewis status and ABO. I found that secretors had significantly higher antibody prevalence and titer to GII NoV than non-secretors suggesting that non-secretors are less prone to be infected by the GII NoV. In Nicaragua, I also found several different NoV strains circulating at the same time. The NoVs have been circulating and evolving in the human population for some time and the same individuals seems to be infected over and over again with the same virus. This suggests that there is no long-term immunity present but possibly short-term immunity, which would make it very difficult to produce a vaccine against NoV. However, recent studies have shown the possibility of using virus like particles as a vaccine candidate and have demonstrated long-term immunity.

    The bovine NoV (boNoV) cause gastroenteritis in cattle and are closely related to the human NoV. The possibility of zoonotic transfer to humans is currently being investigated. I found that 26% of Swedish blood donors have antibodies to the boNoV suggesting that they have been exposed to the virus. The human NoV has been observed to be able to infect and cause disease in cattle, could the boNoV do the same in humans? To date, no boNoV strain has been found in humans. The proposed receptor structure for boNoV is the αGal epitope, which is present in many mammals like cow, pig, horse, sheep and rabbit but not in humans. This indicates that humans are not at risk for boNoV infection because we lack the proper receptor structure. However, recombinations between different NoV strains have been demonstrated and the possibility of more than one receptor being present has been suggested. I found that aa position 365-379 on the boNoV capsid seems to be important for binding to erythrocytes. In this thesis, I hope to add some new pieces to the Norovirus Puzzle.

    List of papers
    1. Antibody Prevalence and Titer to Norovirus (Genogroup II) Correlate with Secretor (FUT2) but Not with ABO Phenotype or Lewis (FUT3) Genotype
    Open this publication in new window or tab >>Antibody Prevalence and Titer to Norovirus (Genogroup II) Correlate with Secretor (FUT2) but Not with ABO Phenotype or Lewis (FUT3) Genotype
    Show others...
    2006 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 194, no 10, p. 1422-1427Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Histo-blood group antigens and secretor status have been associated with susceptibility to Norovirus infections, which suggests that antibody prevalence and titer might correlate with these phenotypes.

    METHODS:

    Plasma samples (n = 105) from Swedish blood donors that had been genotyped for secretor (FUT2) and Lewis (Le; FUT3) genotypes and phenotyped for ABO and Le blood groups were analyzed for immunoglobulin G antibody prevalence and titers to norovirus genogroup (GG) II.4.

    RESULTS:

    The results showed that nonsecretors (se4128se428) and Lea+b- individuals not only had significantly lower antibody titers than did secretors (P < .0001) and Lea-b+ individuals (P < .0002) but were also significantly more often antibody negative (P < .05). Antibody titers in secretors were not significantly different between individuals of different Le (FUT3) genotypes or different ABO phenotypes.

    CONCLUSIONS:

    Nonsecretors and Lea+b- individuals are significantly less prone to be infected with GGII noroviruses. This new information extends previous knowledge and supports the hypothesis that nonsecretors are relatively but not absolutely resistant to norovirus infections.

    Place, publisher, year, edition, pages
    Oxford University Press, 2006
    Keywords
    norovirus
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-68382 (URN)10.1086/508430 (DOI)000241820500011 ()
    Available from: 2011-05-23 Created: 2011-05-23 Last updated: 2018-01-12
    2. Genetic susceptibility to symptomatic norovirus infection in Nicaragua
    Open this publication in new window or tab >>Genetic susceptibility to symptomatic norovirus infection in Nicaragua
    Show others...
    2009 (English)In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 81, no 4, p. 728-735Article in journal (Refereed) Published
    Abstract [en]

    Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2009
    Keywords
    secretors status; Lewis phenotype; blood groups; Norovirus genogroups
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-68384 (URN)10.1002/jmv.21426 (DOI)000263765900022 ()
    Available from: 2011-05-23 Created: 2011-05-23 Last updated: 2018-01-12
    3. Human Antibody Responses to Bovine (Newbury-2) Norovirus (GIII.2) and Association to Histo-Blood Group Antigens
    Open this publication in new window or tab >>Human Antibody Responses to Bovine (Newbury-2) Norovirus (GIII.2) and Association to Histo-Blood Group Antigens
    Show others...
    2010 (English)In: JOURNAL OF MEDICAL VIROLOGY, ISSN 0146-6615, Vol. 82, no 7, p. 1241-1246Article in journal (Refereed) Published
    Abstract [en]

    Serum antibodies to bovine norovirus have been found recently in about 22% of humans. Whether this prevalence reflects limited virulence properties of the virus or that inherited host factors provide protection against bovine norovirus infection in humans remains to be established. To investigate whether histo-blood group antigens correlate with the presence of bovine norovirus (GIII.2) antibody, plasma (n = 105) from Swedish blood donors, genotyped and phenotyped for secretor, Lewis and ABO, were tested and compared for the frequency of IgG antibody and antibody titer to Bo/Newbury2/76/UK. In total, 26.7% (28/105) of Swedish blood donors were antibody-positive. Two non-secretors (2/21, 9.5%) were antibody-positive compared with 26/84 (31%) secretors (P=0.047). While no statistically significant correlation was found between the frequency of antibodies to bovine norovirus and different ABO blood groups, individuals with blood type B presented the highest frequency of antibodies (37.5%) compared with 0-30% among other blood groups. Individuals with Le(a-b+) had not only higher frequency of antibodies (31.3%) compared with Le(a+b-) (11%) (P=0.068) but also higher antibody titer (P=0.085) although this was not significant statistically. No detectable cross-reaction between bovine GIII.2 and human GII.3 NoV VLP was found with human and animal sera. The results of this study suggest that bovine norovirus infections occur in Sweden and that secretor status but not ABO blood groups is a possible risk factor for infection.

    Place, publisher, year, edition, pages
    John Wiley and Sons, Ltd, 2010
    Keywords
    secretor status, blood groups, bovine norovirus, histo-blood group antigens, fucosyltransferase
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-57400 (URN)10.1002/jmv.21776 (DOI)000278173400021 ()
    Available from: 2010-06-18 Created: 2010-06-18 Last updated: 2011-06-01
    4. Characterization of the Bovine Norovirus hemagglutinin
    Open this publication in new window or tab >>Characterization of the Bovine Norovirus hemagglutinin
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    In this study we have analyzed the hemagglutination properties of bovine norovirus GIII.2 Newbury-2 virus like particles (VLPs). Hemagglutination (HA) and hemagglutination inhibition (HI) characteristics were investigated and results showed that bovine norovirus hemagglutinated bovine (6/8), pig (9/9) and rabbit (2/3) red blood cells (RBCs) but not RBC from goat, horse, guinea pig, sheep, chicken or humans. HA capacity differed between calfs and was temperature (4-22°C) and pH (4-10) independent. While three synthetic peptides constructed from the P-region of the capsid could not inhibit HA, a rabbit-peptide antiserum towards aa 365-379 inhibited HA. By homology modeling the bovine NoV shows a deletion close to the ligand binding site for Norwalk. This deletion may be responsible for the different binding patterns of the two strains. The peptide 365-379 was surface exposed and possibly located in a binding pocket. A set of 12 glycoconjugates including the proposed bovine receptor αGal1-3β1-4GlcNAc revealed that none could inhibit hemagglutination although αGal could bind the boVLPS. Neuraminidase did not affect HA suggesting that sialic acid is not a constituent of the HA receptor interaction. Trypsin-treatment of bovine RBCs increased HA titers and treatment with αgalactosidase of trypsin treated and non-trypsin treated RBCs eliminated HA activity suggesting that the αGal epitope is a potential receptor structure that might be connected to a glycolipid.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-68746 (URN)
    Available from: 2011-06-01 Created: 2011-06-01 Last updated: 2011-06-01Bibliographically approved
  • 106.
    Vildevall, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Charpilienne, Annie
    Virologie Moléculaire et Structurale, UMR CNRS, 2472, INRA, 1157, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Nasir, Waqas
    Departement of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Larson, Göran
    Departement of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Characterization of the Bovine Norovirus hemagglutininManuscript (preprint) (Other academic)
    Abstract [en]

    In this study we have analyzed the hemagglutination properties of bovine norovirus GIII.2 Newbury-2 virus like particles (VLPs). Hemagglutination (HA) and hemagglutination inhibition (HI) characteristics were investigated and results showed that bovine norovirus hemagglutinated bovine (6/8), pig (9/9) and rabbit (2/3) red blood cells (RBCs) but not RBC from goat, horse, guinea pig, sheep, chicken or humans. HA capacity differed between calfs and was temperature (4-22°C) and pH (4-10) independent. While three synthetic peptides constructed from the P-region of the capsid could not inhibit HA, a rabbit-peptide antiserum towards aa 365-379 inhibited HA. By homology modeling the bovine NoV shows a deletion close to the ligand binding site for Norwalk. This deletion may be responsible for the different binding patterns of the two strains. The peptide 365-379 was surface exposed and possibly located in a binding pocket. A set of 12 glycoconjugates including the proposed bovine receptor αGal1-3β1-4GlcNAc revealed that none could inhibit hemagglutination although αGal could bind the boVLPS. Neuraminidase did not affect HA suggesting that sialic acid is not a constituent of the HA receptor interaction. Trypsin-treatment of bovine RBCs increased HA titers and treatment with αgalactosidase of trypsin treated and non-trypsin treated RBCs eliminated HA activity suggesting that the αGal epitope is a potential receptor structure that might be connected to a glycolipid.

  • 107.
    Vildevall, Malin
    et al.
    Sahlgrensha University Hospital.
    Oliver, Stefan L
    University of London Royal Veterinary College.
    Bridger, Janice C
    University of London Royal Veterinary College.
    Charpilienne, Annie
    CNRS.
    Poncet, Didier
    CNRS.
    Larson, Goran
    Sahlgrensha University Hospital.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Human Antibody Responses to Bovine (Newbury-2) Norovirus (GIII.2) and Association to Histo-Blood Group Antigens2010In: JOURNAL OF MEDICAL VIROLOGY, ISSN 0146-6615, Vol. 82, no 7, p. 1241-1246Article in journal (Refereed)
    Abstract [en]

    Serum antibodies to bovine norovirus have been found recently in about 22% of humans. Whether this prevalence reflects limited virulence properties of the virus or that inherited host factors provide protection against bovine norovirus infection in humans remains to be established. To investigate whether histo-blood group antigens correlate with the presence of bovine norovirus (GIII.2) antibody, plasma (n = 105) from Swedish blood donors, genotyped and phenotyped for secretor, Lewis and ABO, were tested and compared for the frequency of IgG antibody and antibody titer to Bo/Newbury2/76/UK. In total, 26.7% (28/105) of Swedish blood donors were antibody-positive. Two non-secretors (2/21, 9.5%) were antibody-positive compared with 26/84 (31%) secretors (P=0.047). While no statistically significant correlation was found between the frequency of antibodies to bovine norovirus and different ABO blood groups, individuals with blood type B presented the highest frequency of antibodies (37.5%) compared with 0-30% among other blood groups. Individuals with Le(a-b+) had not only higher frequency of antibodies (31.3%) compared with Le(a+b-) (11%) (P=0.068) but also higher antibody titer (P=0.085) although this was not significant statistically. No detectable cross-reaction between bovine GIII.2 and human GII.3 NoV VLP was found with human and animal sera. The results of this study suggest that bovine norovirus infections occur in Sweden and that secretor status but not ABO blood groups is a possible risk factor for infection.

  • 108.
    Wallensten, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Influenza A virus in wild birds2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Influenza virus is a RNA virus that exists as different types and subtypes. Influenza A virus strains are known to cause disease in several bird and mammalian species. Wild birds are believed to constitute the natural reservoir for influenza A virus.

    In humans, influenza A virus causes yearly seasonal influenza epidemics of respiratory disease resulting in high morbidity and severe economic consequences. Due to the virus’ ability to change its antigenic properties by mutation, yearly vaccination is required for protection from the disease.

    There are many different subtypes of influenza virus which are characterized according to two surface structures - the hemagglutinin and neuraminidase proteins - , for example; H5N1. These subtypes have the ability to recombine, and thereby creating new variant combinations. If a subtype that the living population of humans has not encountered before starts to spread among humans, it can result in a pandemic. Pandemic outbreaks have occurred at irregular intervals throughout history and have had a devastating impact on mankind. For example the Spanish influenza pandemic of 1918 is thought to have killed more than 50 million people.

    Influenza A virus is also an important cause of disease in poultry where virus strains of some subtypes may change into forms that are highly pathogenic. These virus strains may transmit directly to man and multiple other species. This has been the case in the ongoing outbreak that started in South East Asia in 2003. All known subtypes of influenza A virus have been isolated from wild birds living in aquatic environments, mainly dabbling ducks. These species are considered to be the reservoir for influenza A virus. The virus causes sub clinical gastrointestinal infection in ducks. High amounts of virus are excreted in the feces and spread via the fecal-oral route through water where it can persist for a prolonged time.

    There are still many unknowns about the ecology of influenza virus in the wild bird reservoir. This thesis includes five articles where data are presented that add new knowledge on this subject. We add proof that wild ducks are indeed the host for most influenza A virus subtypes by presenting data from a meta-analysis on all published screening data from wild birds and by presenting data from a four year screening of migratory ducks that were caught and sampled at Ottenby Bird Observatory. Our investigations have shown that the prevalence of influenza virus in the wild duck population of western Eurasia shows temporal differences in comparison to the results found in studies in North America. The prevalence in western Eurasian ducks is high during the period August to December and also rises in the spring. These findings are of importance for the understanding of how influenza virus is perpetuated in nature. During the course of the study only low pathogenic subtypes were isolated. Of concern is the high frequency of isolation of virus strains of the H5 and H7 subtypes that are prone to change into highly pathogenic variants in poultry. Many of the strains isolated in our study are similar to the ones that have caused influenza outbreaks in poultry in Europe during the last seven years. This indicates that wild bird surveillance for influenza A virus can be of major value as a sentinel system to prevent outbreaks in domestic poultry.

    Studies on Black-headed Gulls (Larus ridibundus) revealed a previously unknown subtype, H16. This finding widened the spectra of known influenza A virus subtypes in nature.

    Influenza A virus was also isolated in samples from Guillemots (Uria aalge) in the Baltic Sea. This was the first time influenza A virus was isolated from this species in Europe. The isolated virus strains contained a mix of genes, some of which must have been derived from influenza A virus strains present in the North American bird population. This finding proves that limited exchanges between the virus strains present on the American and the Eurasian continents exist, which is of concern for evaluating the risk of spread of highly pathogenic virus strains by wild birds to the Americas.

    List of papers
    1. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from Black-headed Gulls
    Open this publication in new window or tab >>Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from Black-headed Gulls
    Show others...
    2005 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 79, no 5, p. 2814-2822Article in journal (Refereed) Published
    Abstract [en]

    In wild aquatic birds and poultry around the world, influenzaA viruses carrying 15 antigenic subtypes of hemagglutinin (HA)and 9 antigenic subtypes of neuraminidase (NA) have been described.Here we describe a previously unidentified antigenic subtypeof HA (H16), detected in viruses circulating in black-headedgulls in Sweden. In agreement with established criteria forthe definition of antigenic subtypes, hemagglutination inhibitionassays and immunodiffusion assays failed to detect specificreactivity between H16 and the previously described subtypesH1 to H15. Genetically, H16 HA was found to be distantly relatedto H13 HA, a subtype also detected exclusively in shorebirds,and the amino acid composition of the putative receptor-bindingsite of H13 and H16 HAs was found to be distinct from that inHA subtypes circulating in ducks and geese. The H16 virusescontained NA genes that were similar to those of other Eurasianshorebirds but genetically distinct from N3 genes detected inother birds and geographical locations. The European gull viruseswere further distinguishable from other influenza A virusesbased on their PB2, NP, and NS genes. Gaining information onthe full spectrum of avian influenza A viruses and creatingreagents for their detection and identification will remainan important task for influenza surveillance, outbreak control,and animal and public health. We propose that sequence analysesof HA and NA genes of influenza A viruses be used for the rapididentification of existing and novel HA and NA subtypes.

    Place, publisher, year, edition, pages
    ASM International, 2005
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14099 (URN)10.1128/JVI.79.5.2814-2822.2005 (DOI)
    Available from: 2006-10-27 Created: 2006-10-27 Last updated: 2017-12-13Bibliographically approved
    2. Multiple gene segment reassortment between Eurasian and American lineages of influenza A virus (H6N2 in Guillemot (Uria aalge)
    Open this publication in new window or tab >>Multiple gene segment reassortment between Eurasian and American lineages of influenza A virus (H6N2 in Guillemot (Uria aalge)
    Show others...
    2005 (English)In: Archives of Virology, ISSN 0304-8608, Vol. 150, no 8, p. 1685-1692Article in journal (Refereed) Published
    Abstract [en]

    Guillemots banded in the northern Baltic Sea were screened for influenza A virus (IAV). Three out of 26 sampled birds tested positive by RT-PCR. Two of these were characterized as subtype H6N2. Phylogenetic analyses showed that five gene segments belonged to the American avian lineage of IAVs, whereas three gene segments belonged to the Eurasian lineage. Our findings indicate that avian IAVs may have a taxonomically wider reservoir spectrum than previously known and we present the first report of a chimeric avian IAV with genes of American and Eurasian origin in Europe.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14100 (URN)10.1007/s00705-005-0543-8 (DOI)
    Available from: 2006-10-27 Created: 2006-10-27
    3. Mallards and highly pathogenic avian influenza ancestral viruses, northern Europe
    Open this publication in new window or tab >>Mallards and highly pathogenic avian influenza ancestral viruses, northern Europe
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    2005 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 11, no 10, p. 1545-1551Article in journal (Refereed) Published
    Abstract [en]

    Outbreaks of highly pathogenic avian influenza (HPAI), which originate in poultry upon transmission of low pathogenic viruses from wild birds, have occurred relatively frequently in the last decade. During our ongoing surveillance studies in wild birds, we isolated several influenza A viruses of hemagglutinin subtype H5 and H7 that contain various neuraminidase subtypes. For each of the recorded H5 and H7 HPAI outbreaks in Europe since 1997, our collection contained closely related virus isolates recovered from wild birds, as determined by sequencing and phylogenetic analyses of the hemagglutinin gene and antigenic characterization of the hemagglutinin glycoprotein. The minor genetic and antigenic diversity between the viruses recovered from wild birds and those causing HPAI outbreaks indicates that influenza A virus surveillance studies in wild birds can help generate prototypic vaccine candidates and design and evaluate diagnostic tests, before outbreaks occur in animals and humans.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14101 (URN)
    Available from: 2006-10-27 Created: 2006-10-27 Last updated: 2017-12-13
    4. Surveillance of Influenza A Virus in Migratory Waterfowl in Northern Europe
    Open this publication in new window or tab >>Surveillance of Influenza A Virus in Migratory Waterfowl in Northern Europe
    Show others...
    2007 (English)In: Emerging Infectious Diseases, Vol. 13, no 3, p. 404-411Article in journal (Refereed) Published
    Abstract [en]

    We conducted large-scale, systematic sampling of influenza type A virus in migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird Observatory, southeast Sweden. As with previous studies, we found a higher prevalence in fall than spring, and among juveniles compared with adults. However, in contrast to other studies, we found that prevalence in spring was sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility that ducks are capable of perpetuating influenza A virus of different subtypes and subtype combinations throughout the year and from 1 year to the next. Isolation of the H5 and H7 subtypes was common, which suggests risk for transmission to sensitive domestic animals such as poultry. We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14102 (URN)
    Available from: 2006-10-27 Created: 2006-10-27
    5. Global patterns of influenza A virus in wild birds
    Open this publication in new window or tab >>Global patterns of influenza A virus in wild birds
    Show others...
    2006 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 312, no 5772, p. 384-388Article in journal (Refereed) Published
    Abstract [en]

    The outbreak of highly pathogenic avian influenza of the H5N1 subtype in Asia, which has subsequently spread to Russia, the Middle East, Europe, and Africa, has put increased focus on the role of wild birds in the persistence of influenza viruses. The ecology, epidemiology, genetics, and evolution of pathogens cannot be fully understood without taking into account the ecology of their hosts. Here, we review our current knowledge on global patterns of influenza virus infections in wild birds, discuss these patterns in the context of host ecology and in particular birds' behavior, and identify some important gaps in our current knowledge.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14103 (URN)10.1126/science.1122438 (DOI)
    Available from: 2006-10-27 Created: 2006-10-27 Last updated: 2017-12-13
  • 109.
    Wallensten, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Influenza virus in wild birds and mammals other than man2007In: Microbiological Ecology in Health and Disease, ISSN 0891-060X, E-ISSN 1651-2235, Vol. 19, no 2, p. 122-139Article, review/survey (Refereed)
    Abstract [en]

    Influenza virus is an RNA virus that exists as different types and subtypes. Influenza A virus strains are known to cause disease in several bird and mammalian species. Wild birds are believed to constitute the natural reservoir for influenza A virus. Influenza A virus has the ability to change through antigenic drift and recombination allowing for the emergence of new strains and subtype combinations. In man influenza A virus causes yearly seasonal epidemics and, at irregular intervals, pandemic outbreaks have had a devastating impact on mankind. For example, the Spanish influenza pandemic of 1918 is thought to have killed more than 50 million people. Influenza A virus is an important cause of disease in poultry, where virus strains of the H5 and H7 subtypes may change into forms that are highly pathogenic. These virus strains may transmit directly to man and multiple other species. This has been the case in the ongoing outbreak that started in South-east Asia in 2003. All known subtypes of influenza A virus have been isolated from wild birds living in aquatic environments, mainly dabbling ducks. This review focuses on what is known about the pathogenicity and spread of influenza A virus in species other than man, with particular emphasis on the wild bird reservoir. © 2007 Taylor & Francis.

  • 110.
    Wallensten, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Munster, Vincent J.
    Department of Virology and National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands.
    Elmberg, Johan
    Department of Mathematics and Natural Sciences, Kristianstad University, Kristianstad, Sweden.
    Osterhaus, Albert D. M. E.
    Department of Virology and National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands.
    Fouchier, Ron A. M.
    Department of Virology and National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands.
    Olsen, Björn
    Department of Infectious Diseases, Umeå University, Umeå, Sweden.
    Multiple gene segment reassortment between Eurasian and American lineages of influenza A virus (H6N2 in Guillemot (Uria aalge)2005In: Archives of Virology, ISSN 0304-8608, Vol. 150, no 8, p. 1685-1692Article in journal (Refereed)
    Abstract [en]

    Guillemots banded in the northern Baltic Sea were screened for influenza A virus (IAV). Three out of 26 sampled birds tested positive by RT-PCR. Two of these were characterized as subtype H6N2. Phylogenetic analyses showed that five gene segments belonged to the American avian lineage of IAVs, whereas three gene segments belonged to the Eurasian lineage. Our findings indicate that avian IAVs may have a taxonomically wider reservoir spectrum than previously known and we present the first report of a chimeric avian IAV with genes of American and Eurasian origin in Europe.

  • 111.
    Wallensten, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Munster, Vincent J.
    Erasmus Medical Center, Rotterdam, the Netherlands.
    Fransson, Thord
    Swedish Museum of Natural History, Stockholm, Sweden.
    Haemig, Paul D.
    Kalmar University, Kalmar, Sweden.
    Karlsson, Malin
    Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Lundkvist, Åke
    Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Osterhaus, Albert D. M. E.
    Erasmus Medical Center, Rotterdam, the Netherlands.
    Stervander, Martin
    Ottenby Bird Observatory, Degerhamn, Sweden.
    Waldenström, Jonas
    Lund University, Lund, Sweden.
    Olsen, Björn
    Umeå University, Umeå, Sweden.
    Latorre-Margalef, Neus
    Kalmar University, Kalmar, Sweden.
    Brytting, Mia
    Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Elmberg, Johan
    Kristianstad University, Kristianstad, Sweden.
    Fouchier, Ron A. M.
    Erasmus Medical Center, Rotterdam, the Netherlands.
    Surveillance of Influenza A Virus in Migratory Waterfowl in Northern Europe2007In: Emerging Infectious Diseases, Vol. 13, no 3, p. 404-411Article in journal (Refereed)
    Abstract [en]

    We conducted large-scale, systematic sampling of influenza type A virus in migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird Observatory, southeast Sweden. As with previous studies, we found a higher prevalence in fall than spring, and among juveniles compared with adults. However, in contrast to other studies, we found that prevalence in spring was sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility that ducks are capable of perpetuating influenza A virus of different subtypes and subtype combinations throughout the year and from 1 year to the next. Isolation of the H5 and H7 subtypes was common, which suggests risk for transmission to sensitive domestic animals such as poultry. We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry.

  • 112.
    Wallensten, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Munster, V.J.
    Department of Virology, National Influenza Center, Erasmus Medical Center, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, Netherlands.
    Karlsson, M.
    Centre for Microbiological Preparedness (KCB), Swedish Institute for Infectious Disease Control (SMI), SE-171 82 Solna, Sweden.
    Lundkvist, A.
    Centre for Microbiological Preparedness (KCB), Swedish Institute for Infectious Disease Control (SMI), SE-171 82 Solna, Sweden.
    Brytting, M.
    Department of Virology, Swedish Institute for Infectious Disease Control (SMI), SE-171 82 Solna, Sweden.
    Stervander, M.
    Ottenby Bird Observatory, P.O. Box 1500, SE-380 65 Degerhamn, Sweden.
    Osterhaus, A.D.M.E.
    Department of Virology, National Influenza Center, Erasmus Medical Center, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, Netherlands.
    Fouchier, R.A.M.
    Department of Virology, National Influenza Center, Erasmus Medical Center, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, Netherlands.
    Olsen, B.
    Department of Infectious Diseases, Umeå University, SE-901 87 Umeå, Sweden, Department of Biology and Environmental Science, Section for Zoonotic Ecology and Epidemiology, Kalmar University, SE-391 82 Kalmar, Sweden.
    High prevalence of influenza A virus in ducks caught during spring migration through Sweden2006In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 24, no 44-46, p. 6734-6735Article in journal (Refereed)
    Abstract [en]

    As part of our ongoing screening of wild birds in Northern Europe, 358 mallards (Anas platyrhynchos) and 203 shelducks (Tadorna tadorna) were caught in southern Sweden during the spring 2003. Faecal samples were analyzed by real time RT-PCR for the presence of influenza A virus. In contrast to what has been found in North American studies, Eurasian spring migrating ducks passing through Sweden had a relatively high prevalence of influenza A virus. © 2006 Elsevier Ltd. All rights reserved.

  • 113.
    Wallensten, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Munster, V.J.
    Department of Virology, National Influenza Center, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE, Rotterdam, Netherlands.
    Osterhaus, A.D.M.E.
    Department of Virology, National Influenza Center, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE, Rotterdam, Netherlands.
    Waldenstrom, J.
    Waldenström, J., Department of Animal Ecology, Ecology Building, Lund University, SE-223 62 Lund, Sweden, Department of Biology and Environmental Science, Section for Zoonotic Ecology and Epidemiology, Kalmar University, SE-391 82 Kalmar, Sweden.
    Bonnedahl, J.
    Department of Infectious Diseases, Umeå University, SE-901 87 Umeå, Sweden.
    Broman, T.
    Department of NBC Analysis, Swedish Defence Research Agency, NBC Defence, SE-901 82 Umeå, Sweden.
    Fouchier, R.A.M.
    Department of Virology, National Influenza Center, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE, Rotterdam, Netherlands.
    Olsen, B.
    Department of Infectious Diseases, Umeå University, SE-901 87 Umeå, Sweden, Department of Biology and Environmental Science, Section for Zoonotic Ecology and Epidemiology, Kalmar University, SE-391 82 Kalmar, Sweden.
    Mounting evidence for the presence of influenza A virus in the avifauna of the Antarctic region2006In: Antarctic Science, ISSN 0954-1020, E-ISSN 1365-2079, Vol. 18, no 3, p. 353-356Article in journal (Refereed)
    Abstract [en]

    Penguin blood samples collected at Bird Island, sub-Antarctic South Georgia, and faecal samples taken from penguins at several localities along the Antarctic Peninsula were analysed in order to investigate if influenza A virus is present in penguin populations in the South Atlantic Antarctic region. Serology was performed on the blood samples while the faecal samples were screened by a RT-PCR method directed at the matrix protein gene for determining the presence of influenza A virus. All faecal samples were negative by PCR, but the blood samples gave serologic indications that influenza A virus is present amongst these penguin species, confirming previous studies, although the virus has still not been isolated from any bird in the Antarctic region. © Antarctic Science Ltd.

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