Browsing by Subject "VIRUS-INFECTION"

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  • Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin; Christensen, Peer Brehm; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Wejstal, Rune; Norkrans, Gunnar; Lindh, Magnus; Farkkila, Martti; Westin, Johan (2014)
  • Okuneva, Olesya; Li, Zhilin; Korber, Inken; Tegelberg, Saara; Joensuu, Tarja; Tian, Li; Lehesjoki, Anna-Elina (2016)
    Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb(-/-)) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb(-/-) mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb(-/-) mice and higher CXCL13 expression in activated microglia in Cstb(-/-) compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb(-/-) mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb(-/-)mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.
  • Koskela, Sirpa M.; Joutsi-Korhonen, Lotta; Mäkelä, Satu M.; Huhtala, Heini; Vaheri, Antti I.; Pörsti, Ilkka; Mustonen, Jukka T.; Laine, Outi K. (2018)
    Coagulation abnormalities are associated with Puumala-virus-induced hemorrhagic fever with renal syndrome (PUUV-HFRS). We evaluated the coagulation capacity of plasma during acute PUUV-HFRS by measuring thrombin generation using calibrated automated thrombography (CAT). The study cohort comprised 27 prospectively collected, consecutive, hospital-treated patients with acute PUUV infection. Blood samples were drawn in the acute phase and at the control visit approximately 5 weeks later. To evaluate thrombin generation, the lag time of initiation, endogenous thrombin potential (ETP), and peak and time to peak thrombin concentration were assessed by CAT in platelet poor plasma without corn trypsin inhibitor. Plasma levels of d-dimer, fibrinogen and prothrombin fragments (F1 + 2) were also evaluated. When the acute phase was compared with the control phase, ETP was decreased (median 1154 nmol/l/min, range 67-1785 vs. median 1385 nmol/l/min, range 670-1970; P <0.001), while the lag time was prolonged (median 3.8 min, range 2.1-7.7 vs. median 2.9 min, range 2.0-4.1; P <0.001). Low ETP correlated with low peak thrombin concentration (r = 0.833, P <0.001). Prolonged time to peak associated with the lag time (r = 0.78, P <0.001). ETP was associated with thrombocytopenia (r = 0.472, P = 0.015) and weakly with fibrinogen level (r = 0.386, P = 0.047). The measured CAT parameters did not associate with d-dimer and F1 + 2 levels. Decreased ETP together with low peak and prolonged lag time indicate decreased plasma potential for thrombin generation in vitro. Together with low platelet count and enhanced fibrinolysis, this further refers to altered blood coagulation and increased propensity toward bleeding in acute PUUV-HFRS. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
  • Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Foersti, Asta; Liska, Vaclav; Hemminki, Akseli; Li, Xinjun (2022)
    Simple Summary Familial risk of cancer implies that two or more family members are diagnosed with the same cancer. This may be due to the genes or environmental factors that family members share. Familial risk for liver and gallbladder cancer is about 2.7 which means that when one family member is diagnosed with these cancers other family members have 2.7 times higher risk of being diagnosed with the same cancers compared to families were no member is yet diagnosed with these cancers. Risk between spouses is entirely due to shared environmental factors and for liver cancer there is a small risk. The most important way to prevent these cancers is to avoid their risk factors, alcohol, smoking and overweight, and to seek medical care for diabetes and liver infections. We used the Swedish Cancer Registry data to address familial risks for concordant (same) and discordant (different) hepatobiliary cancers, including their associations with any other cancers and with known risk factors. Risks were also assessed between spouses. The analysis covered Swedish families and their cancers between years 1958 and 2018. Adjusted familial risks were expressed as standardized incidence ratios (SIRs). Familial SIRs for concordant hepatocellular carcinoma (HCC) were 2.60, and for gallbladder cancer they were at the same level (2.76). Familial risk was also found for intrahepatic bile duct cancer and for female extrahepatic bile duct cancer. HCC was associated with lung and cervical cancers; extrahepatic bile duct and ampullary cancers were associated with colon and pancreatic cancers, suggesting Lynch syndrome. Among spouses, hepatobiliary cancer was associated with HCC, stomach, pancreatic, cervical and upper aerodigestive tract cancers. Among risk factors, family members diagnosed with alcohol-related disease showed association with HCC. The observed familial risks for hepatobiliary cancers were relatively high, and considering the poor prognosis of these cancers, prevention is of the utmost importance and should focus on moderation of alcohol consumption, vaccination/treatment of hepatitis viral infections and avoidance of overweight and other risk factors of type 2 diabetes.
  • Ling, Jiaxin; Verner-Carlsson, Jenny; Eriksson, Per; Plyusnina, Angelina; Loehmus, Mare; Jaerhult, Josef D.; van de Goot, Frank; Plyusnin, Alexander; Lundkvist, Ake; Sironen, Tarja (2019)
    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.
  • Einarsdottir, Elisabet; Hafren, Lena; Leinonen, Eira; Bhutta, Mahmood F.; Kentala, Erna; Kere, Juha; Mattila, Petri S. (2016)
    To identify genetic risk factors of childhood otitis media (OM), a genome-wide association study was performed on Finnish subjects, 829 affected children, and 2118 randomly selected controls. The most significant and validated finding was an association with an 80 kb region on chromosome 19. It includes the variants rs16974263 (P = 1.77 x 10(-7), OR = 1.59), rs268662 (P = 1.564 x 10(-6), OR = 1.54), and rs4150992 (P = 3.37 x 10(-6), OR = 1.52), and harbors the genes PLD3, SERTAD1, SERTAD3, HIPK4, PRX, and BLVRB, all in strong linkage disequilibrium. In a sub-phenotype analysis of the 512 patients with chronic otitis media with effusion, one marker reached genome-wide significance (rs16974263, P = 2.92 x 10(-8)). The association to this locus was confirmed but with an association signal in the opposite direction, in a UK family cohort of 4860 subjects (rs16974263, P = 3.21 x 10(-4), OR = 0.72; rs4150992, P = 1.62 x 10(-4), OR = 0.71). Thus we hypothesize that this region is important for COME risk in both the Finnish and UK populations, although the precise risk variants or haplotype background remain unclear. Our study suggests that the identified region on chromosome 19 includes a novel and previously uncharacterized risk locus for OM.
  • Rembeck, Karolina; Alsio, Asa; Christensen, Peer Brehm; Färkkilä, Martti Antero; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Westin, Johan; Lindh, Magnus; Hellstrand, Kristoffer; Norkrans, Gunnar; Lagging, Martin (2012)
  • Alsio, Asa; Rembeck, Karolina; Askarieh, Galia; Christensen, Peer Brehm; Färkkilä, Martti Antero; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Haagmans, Bart L.; Nasic, Salmir; Westin, Johan; Hellstrand, Kristoffer; Norkrans, Gunnar; Lagging, Martin (2012)
  • Ghafari, Mahan; Lumby, Casper K.; Weissman, Daniel B.; Illingworth, Christopher J. R. (2020)
    The transmission bottleneck is defined as the number of viral particles that transmit from one host to establish an infection in another. Genome sequence data have been used to evaluate the size of the transmission bottleneck between humans infected with the influenza virus; however, the methods used to make these estimates have some limitations. Specifically, viral allele frequencies, which form the basis of many calculations, may not fully capture a process which involves the transmission of entire viral genomes. Here, we set out a novel approach for inferring viral transmission bottlenecks; our method combines an algorithm for haplotype reconstruction with maximum likelihood methods for bottleneck inference. This approach allows for rapid calculation and performs well when applied to data from simulated transmission events; errors in the haplotype reconstruction step did not adversely affect inferences of the population bottleneck. Applied to data from a previous household transmission study of influenza A infection, we confirm the result that the majority of transmission events involve a small number of viruses, albeit with slightly looser bottlenecks being inferred, with between 1 and 13 particles transmitted in the majority of cases. While influenza A transmission involves a tight population bottleneck, the bottleneck is not so tight as to universally prevent the transmission of within-host viral diversity. IMPORTANCE Viral populations undergo a repeated cycle of within-host growth followed by transmission. Viral evolution is affected by each stage of this cycle. The number of viral particles transmitted from one host to another, known as the transmission bottleneck, is an important factor in determining how the evolutionary dynamics of the population play out, restricting the extent to which the evolved diversity of the population can be passed from one host to another. Previous study of viral sequence data has suggested that the transmission bottleneck size for influenza A transmission between human hosts is small. Reevaluating these data using a novel and improved method, we largely confirm this result, albeit that we infer a slightly higher bottleneck size in some cases, of between 1 and 13 virions. While a tight bottleneck operates in human influenza transmission, it is not extreme in nature; some diversity can be meaningfully retained between hosts.
  • EuroSIDA study; Mocroft, Amanda; Lundgren, Jens D.; Rockstroh, Juergen K.; Aho, Inka; Peters, Lars (2020)
    Background. The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. Methods. Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (antiHCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). Results. A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNApositive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM. Conclusions. HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.
  • Fevola, Cristina; Forbes, Kristian M.; Makela, Satu; Putkuri, Niina; Hauffe, Heidi C.; Kallio-Kokko, Hannimari; Mustonen, Jukka; Jaaskelainen, Anne J.; Vaheri, Antti (2016)
    Background: The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus. Objective: The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity. Study design: We evaluated seroprevalence of and seroconversions to LCMV, LV and OPV in 116 patients hospitalized for NE. Clinical and laboratory variables were closely monitored during hospital care. Results: A total of five LCMV, 15 LV, and one OPV seroconversions occurred. NE patients with LCMV seroconversions were younger, and had lower plasma creatinine concentrations and platelet counts than patients without LCMV seroconversions. No differences occurred in clinical or laboratory findings between patients with and without seroconversions to LV and OPV. We report, for the first time, LCMV seroprevalence in Finland, with 8.5% of NE patients seropositive for this virus. Seroprevalences for LV and OPV were 47.8% and 32.4%, respectively. Conclusion: Cases with LCMV seroconversions were statistically younger, had milder acute kidney injury and more severe thrombocytopenia than patients without LCMV. However, the low number of seroconversion cases precludes firm conclusions. Concurrent LV or OPV infections do not appear to influence clinical picture for NE patients. (C) 2016 Elsevier B.V. All rights reserved.
  • Stanelle-Bertram, Stephanie; Walendy-Gnirss, Kerstin; Speiseder, Thomas; Thiele, Swantje; Asante, Ivy Asantewaa; Dreier, Carola; Kouassi, Nancy Mounogou; Preuss, Annette; Pilnitz-Stolze, Gundula; Mueller, Ursula; Thanisch, Stefanie; Richter, Melanie; Scharrenberg, Robin; Kraus, Vanessa; Doerk, Ronja; Schau, Lynn; Herder, Vanessa; Gerhauser, Ingo; Pfankuche, Vanessa Maria; Kaeufer, Christopher; Waltl, Inken; Moraes, Thais; Sellau, Julie; Hoenow, Stefan; Schmidt-Chanasit, Jonas; Jansen, Stephanie; Schattling, Benjamin; Ittrich, Harald; Bartsch, Udo; Renne, Thomas; Bartenschlager, Ralf; Arck, Petra; Cadar, Daniel; Friese, Manuel A.; Vapalahti, Olli; Lotter, Hanna; Benites, Sany; Rolling, Lane; Gabriel, Martin; Baumgaertner, Wolfgang; Morellini, Fabio; Hoelter, Sabine M.; Amarie, Oana; Fuchs, Helmut; de Angelis, Martin Hrabe; Loescher, Wolfgang; de Anda, Froylan Calderon; Gabriel, Guelsah (2018)
    Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.
  • Nyman, Tuula A.; Lorey, Martina B.; Cypryk, Wojciech; Matikainen, Sampsa (2017)
    Introduction: The immune system is our defense system against microbial infections and tissue injury, and understanding how it works in detail is essential for developing drugs for different diseases. Mass spectrometry-based proteomics can provide in-depth information on the molecular mechanisms involved in immune responses.Areas covered: Summarized are the key immunology findings obtained with MS-based proteomics in the past five years, with a focus on inflammasome activation, global protein secretion, mucosal immunology, immunopeptidome and T cells. Special focus is on extracellular vesicle-mediated protein secretion and its role in immune responses.Expert commentary: Proteomics is an essential part of modern omics-scale immunology research. To date, MS-based proteomics has been used in immunology to study protein expression levels, their subcellular localization, secretion, post-translational modifications, and interactions in immune cells upon activation by different stimuli. These studies have made major contributions to understanding the molecular mechanisms involved in innate and adaptive immune responses. New developments in proteomics offer constantly novel possibilities for exploring the immune system. Examples of these techniques include mass cytometry and different MS-based imaging approaches which can be widely used in immunology.
  • Ylösmäki, Erkko; Lavilla Alonso, Sergio; Jäämaa, Sari Susanna; Vaha-Koskela, Markus; af Hällström, Taija Maria; Hemminki, Akseli; Arola, Johanna; Mäkisalo, Heikki; Saksela, Kalle (2013)
  • Ianevski, Aleksandr; Yao, Rouan; Simonsen, Ronja M.; Myhre, Vegard; Ravlo, Erlend; Kaynova, Gerda D.; Zusinaite, Eva; White, Judith M.; Polyak, Stephen J.; Oksenych, Valentyn; Windisch, Marc P.; Pan, Qiuwei; Lastauskiene, Egle; Vitkauskiene, Astra; Matukevicius, Algimantas; Tenson, Tanel; Bjoras, Magnar; Kainov, Denis E. (2022)
    Broadly effective antiviral therapies must be developed to be ready for clinical trials, which should begin soon after the emergence of new life-threatening viruses. Here, we pave the way towards this goal by reviewing conserved druggable virus-host interactions, mechanisms of action, immunomodulatory properties of available broad-spectrum antivirals (BSAs), routes of BSA delivery, and interactions of BSAs with other antivirals. Based on the review, we concluded that the range of indications of BSAs can be expanded, and new pan- and cross-viral mono- and combinational therapies can be developed. We have also developed a new scoring algorithm that can help identify the most promising few of the thousands of potential BSAs and BSA-containing drug cocktails (BCCs) to prioritize their development during the critical period between the identification of a new virus and the development of virus-specific vaccines, drugs, and therapeutic antibodies.
  • Strandin, Tomas; Smura, Teemu; Ahola, Paula; Aaltonen, Kirsi; Sironen, Tarja; Hepojoki, Jussi; Eckerle, Isabella; Ulrich, Rainer G.; Vapalahti, Olli; Kipar, Anja; Forbes, Kristian M. (2020)
    Orthohantaviruses are globally emerging zoonotic pathogens. While the reservoir host role of several rodent species is well-established, detailed research on the mechanisms of host-othohantavirus interactions has been constrained by the lack of an experimental system that is able to effectively replicate natural infections in controlled settings. Here we report the isolation, and genetic and phenotypic characterization of a novel Puumala orthohantavirus (PUUV) in cells derived from its reservoir host, the bank vole. The isolation process resulted in cell culture infection that evaded antiviral responses, persisted cell passaging, and had minor viral genome alterations. Critically, experimental infections of bank voles with the new isolate resembled natural infections in terms of viral load and host cell distribution. When compared to an attenuated Vero E6 cell-adapted PUUV Kazan strain, the novel isolate demonstrated delayed virus-specific humoral responses. A lack of virus-specific antibodies was also observed during experimental infections with wild-type PUUV, suggesting that delayed seroconversion could be a general phenomenon during orthohantavirus infection in reservoir hosts. Our results demonstrate that orthohantavirus isolation on cells derived from a vole reservoir host retains wild-type infection properties and should be considered the method of choice for experimental infection models to replicate natural processes.
  • Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Liska, Vaclav; Hemminki, Akseli; Li, Xinjun (2023)
    Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.
  • Outinen, Tuula K.; Kuparinen, Taru; Jylhava, Juulia; Leppanen, Sonja; Mustonen, Jukka; Makela, Satu; Porsti, Ilkka; Syrjanen, Jaana; Vaheri, Antti; Hurme, Mikko (2012)
  • Outinen, Tuula K.; Tervo, Laura; Makela, Satu; Huttunen, Reetta; Maenpaa, Niina; Huhtala, Heini; Vaheri, Antti; Mustonen, Jukka; Aittoniemi, Janne (2013)
  • Hep-Nordic Study Grp (2018)
    Background and aims In the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden), the prevalence of chronic hepatitis C virus (HCV) infection is relatively low in the general population, but is much higher among people who inject drugs (PWID). We conducted an exploratory study to investigate the extent to which these countries have policies supporting key elements of the public health response that is necessary to achieve the global goal of eliminating HCV as a public health threat. Methods Fourteen stakeholders representing government agencies, medical societies, and civil society organisations (CSOs) in the Nordic countries completed a cross-sectional online survey that included 21 policy questions related to national coordination, prevention, testing, linkage to care, and treatment. We summarised the findings in a descriptive analysis, and noted discrepant responses from stakeholders within the same country. Results Stakeholders reported that three of the five study countries have national viral hepatitis strategies, while only Iceland has a national HCV elimination goal. The availability of harm reduction services varies, with opioid substitution therapy provided for the general population throughout all countries, but not needle and syringe programmes. No country has access to anonymous HCV testing in all parts of the country. National HCV treatment guidelines are available in all countries except Finland, and all countries provide publicly funded direct-acting antiviral treatment. Disagreement regarding policies was observed across countries, and CSOs were the stakeholder group that most frequently answered survey questions incorrectly. Conclusion The Nordic region as a whole has not consistently expressed its commitment to tackling HCV, despite the existence of large HCV epidemics among PWID in these countries. Stakeholder alignment and an established elimination goal with an accompanying strategy and implementation plan should be recognised as the basis for coordinated national public health efforts to achieve HCV elimination in the Nordic region and elsewhere.