Browsing by Subject "OUTBREAK"

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  • Österlund, Pamela; Jiang, Miao; Westenius, Veera; Kuivanen, Suvi; Järvi, Riia; Kakkola, Laura; Lundberg, Rickard; Melen, Krister; Korva, Misa; Avsic-Zupanc, Tatjana; Vapalahti, Olli; Julkunen, Ilkka (2019)
    Zika virus (ZIKV) infections in humans are considered to be mild or subclinical. However, during the recent epidemics in the Pacific Islands and the Americas, the infection was associated with Quillain-Barre syndrome and congenital infections with fetal brain abnormalities, including microcephaly. Thus, more detailed understanding of ZIKV-host cell interactions and regulation of innate immune responses by strains of differential evolutionary origin is required. Here, we characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells (DCs) and macrophages. The epidemic Asian/American ZIKV replicated well and induced relatively good antiviral responses in human DCs whereas the African strain replicated less efficiently and induced weaker immune responses. In macrophages both the African and Asian strains showed limited replication and relatively weak cytokine gene expression. Interestingly, in macrophages we observed host protein degradation, especially IRF3 and STAT2, at early phases of infection with both lineage viruses, suggesting an early proteasomal activation in phagocytic cells. Our data indicates that ZIKV evolution has led to significant phenotypic differences in the replication characteristics leading to differential regulation of host innate immune responses.
  • Vähänikkilä, N.; Pohjanvirta, T.; Haapala, V.; Simojoki, H.; Soveri, T.; Browning, G. F.; Pelkonen, S.; Wawegama, N. K.; Autio, T. (2019)
    Mycoplasma bovis causes bovine respiratory disease, mastitis, arthritis and otitis. The importance of M. bovis has escalated because of recent outbreaks and introductions into countries previously free of M. bovis. We characterized the course of M. bovis infection on 19 recently infected dairy farms over 24 months. Our objective was to identify diagnostic tools to assess the efficacy of control measures to assess low risk infection status on M. bovis infected farms. PCR assays and culture were used to detect M. bovis, and in-house and BioX ELISAs were used to follow antibody responses. Cows and young stock were sampled on four separate occasions, and clinical cases were sampled when they arose. On 17 farms, a few cases of clinical mastitis were detected, mostly within the first eight weeks after the index case. Antibodies detected by in-house ELISA persisted in the serum of cows at least for 1.5 years on all farms, regardless of the M. bovis infection status or signs of clinical disease or subclinical mastitis on the farm. Six out of 19 farms became low risk as the infection was resolved. Our results suggest that, for biosecurity purposes, regular monitoring should be conducted on herds by screening for M. bovis in samples from cows with clinical mastitis and calves with pneumonia, in conjunction with testing young stock by screening longitudinally collected nasal swabs for M. bovis and sequential serum samples for antibody against recombinant antigen.
  • Lienemann, Taru; Kyyhkynen, Aino; Halkilahti, Jani; Haukka, Kaisa; Siitonen, Anja (2015)
    Background: Salmonella enterica spp. enterica serotype Typhimurium (STM) is the most common agent of domestically acquired salmonellosis in Finland. Subtyping methods which allow the characterization of STM are essential for effective laboratory-based STM surveillance and for recognition of outbreaks. This study describes the diversity of Finnish STM isolates using phage typing, antimicrobial susceptible testing, pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem repeat analysis (MLVA), and compares the discriminatory power and the concordance of these methods. Results: A total of 375 sporadic STM isolates were analysed. The isolates were divided into 31 definite phage (DT) types, dominated by DT1 (47 % of the isolates), U277 (9 % of the isolates) and DT104 (8 % of the isolates). Of all the isolates, 62 % were susceptible to all the 12 antimicrobials tested and 11 % were multidrug resistant. Subtyping resulted in 83 different XbaI-PFGE profiles and 111 MLVA types. The three most common XbaI-PFGE profiles (STYM1, STYM7 and STYM8) and one MLVA profile with three single locus variants accounted for 56 % and 49 % of the STM isolates, respectively. The studied isolates showed a genetic similarity of more than 70 % by XbaI-PFGE. In MLVA, 71 % of the isolates lacked STTR6 and 77 % missed STTR10p loci. Nevertheless, the calculated Simpson's diversity index for XbaI-PFGE was 0.829 (95 % CI 0.792-0.865) and for MLVA 0.867 (95 % CI 0.835-0.898). However, the discriminatory power of the 5-loci MLVA varied among the phage types. The highest concordance of the results was found between XbaI-PFGE and phage typing (adjusted Wallace coefficient was 0.833 and adjusted Rand coefficient was 0.627). Conclusions: In general, the calculated discriminatory power was higher for genotyping methods (MLVA and XbaI-PFGE) than for phenotyping methods (phage typing). Overall, comparable diversity indices were calculated for PFGE and MLVA (both DI > 0.8). However, MLVA was phage type dependent providing better discrimination of the most common phage types. Furthermore, 5-loci MLVA was a less laborious method and easier to interpret than XbaI-PFGE. Thus, the laboratory-based surveillance of the Finnish human STM infections has been conducted with a combination of phage typing, antimicrobial susceptibility testing and 5-loci MLVA since January 2014.
  • McNally, Alan; Oren, Yaara; Kelly, Darren; Pascoe, Ben; Dunn, Steven; Sreecharan, Tristan; Vehkala, Minna; Välimäki, Niko; Prentice, Michael B.; Ashour, Amgad; Avram, Oren; Pupko, Tal; Dobrindt, Ulrich; Literak, Ivan; Guenther, Sebastian; Schaufler, Katharina; Wieler, Lothar H.; Zong Zhiyong,; Sheppard, Samuel K.; McInerney, James O.; Corander, Jukka (2016)
    The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug-resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.
  • Jaakkola, Kaisa; Somervuo, Panu; Korkeala, Hannu (2015)
    Enteropathogenic Yersinia enterocolitica and Yersinia pseudotuberculosis are both etiological agents for intestinal infection known as yersiniosis, but their epidemiology and ecology bearmany differences. Swine are the only known reservoir for Y. enterocolitica 4/O:3 strains, which are the most common cause of human disease, while Y. pseudotuberculosis has been isolated from a variety of sources, including vegetables and wild animals. Infections caused by Y. enterocolitica mainly originate froms wine, but fresh produce has been the source for widespread Y. pseudotuberculosis outbreaks within recent decades. A comparative genomic hybridization analysis with a DNA microarray based on three Yersinia enterocolitica and four Yersinia pseudotuberculosis genomes was conducted to shed light on the genomic differences between enteropathogenic Yersinia. The hybridization results identified Y. pseudotuberculosis strains to carry operons linked with the uptake and utilization of substances not found in living animal tissues but present in soil, plants, and rotting flesh. Y. pseudotuberculosis also harbors a selection of type VI secretion systems targeting other bacteria and eukaryotic cells. These genetic traits are not found in Y. enterocolitica, and it appears that while Y. pseudotuberculosis has many tools beneficial for survival in varied environments, the Y. enterocolitica genome is more streamlined and adapted to their preferred animal reservoir.
  • Virtanen, Sonja; Kapp, Karmen; Rautamo, Maria M; Lotta, Schepel; Linden-Lahti, Carita; Cruz, Cristina D.; Tammela, Päivi (2021)
    Parenteral products must be compounded using an aseptic technique to ensure sterility of the medicine. We compared the effect of three clinical environments as compounding areas as well as different aseptic techniques on the sterility of the compounded parenteral product. Clinical pharmacists and pediatric nurses compounded 220 samples in total in three clinical environments: a patient room, a medicine room and biological safety cabinet. The study combined four methods: observation, environmental monitoring (settle plates), monitoring of personnel (finger dab plates) and sterility testing (membrane filtration). Of the compounded samples, 99% were sterile and no significant differences emerged between the clinical environments. Based on the settle plates, the biological safety cabinet was the only area that fulfilled the requirements for eliminating microbial contamination. Most of the steps on the observation form for aseptic techniques were followed. All participants disinfected their hands, wore gloves and disinfected the septum of the vial. Non-contaminated finger dab plates were mostly detected after compounding in the biological safety cabinet. Aseptic techniques were followed relatively well in all environments. However, these results emphasize the importance of good aseptic techniques and support the recommendation of compounding parenteral products in biological safety cabinets in clinical environments.
  • Oristo, Satu; Rönnqvist, Maria; Aho, Mika; Sovijärvi, Ava; Hannila-Handelberg, Tuula; Horman, Ari; Nikkari, Simo; Kinnunen, Paula M.; Maunula, Leena (2017)
    This study investigated the presence of norovirus and adenovirus, especially enteric adenovirus, on the environmental surfaces (n = 481) and military conscripts' hands (n = 109) in two Finnish garrisons (A and B) in 2013 and 2014. A questionnaire study was conducted to reveal possible correlations between viral findings on the conscripts' hands and their acute gastroenteritis symptoms. In addition to the swab samples, 14 fecal samples were obtained for viral analysis. In total, norovirus was present in 9.0 % of the surface swabs in 2013, whereas enteric adenovirus was present in 0.0 % and non-enteric adenovirus in 9.4 %. In the same year, 2.6 % of the hand swabs contained norovirus, 2.6 % enteric adenovirus, and 40.3 % non-enteric adenovirus. Norovirus GI.6 was continually detected on the surfaces of garrison A, and identical virus was detected in some of the fecal samples. In garrison B, two slightly different norovirus GII.4 strains were present on the surfaces. The questionnaires revealed no recent acute gastroenteritis cases in garrison A, but in garrison B, where the norovirus-positive hand swabs were collected, 30.6 % of the conscripts reported of recent symptoms. In 2014, norovirus was rarely detected, but adenovirus was again frequently present, both on the surfaces and hands. Taken together, our results suggest that gastroenteritis outbreaks occurred in 2013, but not in 2014. Due to the low number of hand swabs positive for enteric viruses, no conclusions about associations between viral findings and gastroenteritis symptoms could be drawn. This study increased our understanding of the possible transmission of viruses via contaminated environment and hands.
  • Kluger, Nicolas (2016)
    Tattooing can result in a wide variety of complications, whose prevalence and incidence remain still unclear. Hypersensitivity reactions (or allergies) to tattoo pigments are currently the most common complication on a tattoo, however they are not predictable. Infections are nowadays directly related to the lack of asepsis and hygiene during the tattooing procedure or during the healing phase. Patients with a known cutaneous disease should be warned of a potential risk of localization of their disease to the tattoo. A skin eruption restricted to a tattoo may reveal sarcoidosis. Patients with chronic conditions and/or impaired immunity should discuss with their physician about the possibility and when to have a tattoo.
  • 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.
  • Mohan, Vathsala; Cruz, Cristina D.; van Vliet, Arnoud H. M.; Pitman, Andrew R.; Visnovsky, Sandra B.; Rivas, Lucia; Gilpin, Brent; Fletcher, Graham C. (2021)
    Listeria monocytogenes is a foodborne human pathogen that causes systemic infection, fetal-placental infection in pregnant women causing abortion and stillbirth and meningoencephalitis in elderly and immunocompromised individuals. This study aimed to analyse L. monocytogenes from different sources from New Zealand (NZ) and to compare them with international strains. We used pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and whole-genome single nucleotide polymorphisms (SNP) to study the population structure of the NZ L. monocytogenes isolates and their relationship with the international strains. The NZ isolates formed unique clusters in PFGE, MLST and whole-genome SNP comparisons compared to the international isolates for which data were available. PFGE identified 31 AscI and 29 ApaI PFGE patterns with indistinguishable pulsotypes being present in seafood, horticultural products and environmental samples. Apart from the Asc0002:Apa0002 pulsotype which was distributed across different sources, other pulsotypes were site or factory associated. Wholegenome analysis of 200 randomly selected L. monocytogenes isolates revealed that lineage II dominated the NZ L. monocytogenes populations. MLST comparison of international and NZ isolates with lineage II accounted for 89% (177 of 200) of the total L. monocytogenes population, while the international representation was 45.3% (1674 of 3473). Rarefaction analysis showed that sequence type richness was greater in NZ isolates compared to international trend, however, it should be noted that NZ isolates predominantly came from seafood, horticulture and their respective processing environments or factories, unlike international isolates where there was a good mixture of clinical, food and environmental isolates.
  • Petersen, Eskild; Kantele, Anu; Koopmans, Marion; Asogun, Danny; Yinka-Ogunleye, Adesola; Ihekweazu, Chikwe; Zumla, Alimuddin (2019)
    Recently, concern has been raised about the emergence of human monkeypox virus and the occasionally severe clinical presentation bearing resemblance to that of smallpox. In 2018, 3 patients in the UK were diagnosed with monkeypox, and the frequency and geographic distribution of cases across West and Central Africa have increased in recent years. In Nigeria, most monkeypox patients are aged
  • Kareinen, Lauri; Hepojoki, Satu; Huhtamo, Eili; Korhonen, Essi M.; Schmidt-Chanasit, Jonas; Hedman, Klaus; Hepojoki, Jussi; Vapalahti, Olli (2019)
    Zika virus (ZIKV) is a mosquito-borne pathogen causing a febrile illness with arthralgia, conjunctivitis and rash. The complications include Guillain-Barré syndrome, congenital brain and other abnormalities and miscarriage. The serodiagnosis of ZIKV infection is hampered by cross-reactivity with other members of the Flavivirus family, notably dengue (DENV). This report describes a novel serological platform for the diagnosis of ZIKV infection. The approach utilizes time-resolved Förster resonance energy transfer (TR-FRET) elicited by two chromophore-labeled proteins (a ZIKV antigen and a super-antigen) simultaneously binding to a given antibody molecule. The antigen used in the assay is ZIKV non-structural protein 1 (NS1) and the super-antigen is bacterial protein L. Three assay variants were developed: the first measuring all anti-ZIKV-NS1 antibodies (LFRET), the second measuring IgM and IgA (acute-LFRET) and the third measuring IgG (immunity-LFRET). The assays were evaluated with a panel of samples from clinical ZIKV cases in travelers (n = 25) and seronegative (n = 24) samples. DENV (n = 38), yellow fever (n = 16) and tick-borne-encephalitis (n = 20) seropositive samples were examined for assessment of flavivirus cross-reactivity. The diagnostic sensitivities of the respective LFRET assays were 92%, 100% and 83%, and the diagnostic specificities 88%, 95% and 100% for LFRET, acute-LFRET and immunity-LFRET. Furthermore, we evaluated the assays against a widely-used commercial ELISA. In conclusion, the new FRET-based serological approaches based on NS1 protein are applicable to diagnosing zika virus infections in travelers and differentiating them from other flavivirus infections.
  • StaphTrav Network; Nurjadi, D.; Fleck, R.; Kantele, A.; Zanger, P. (2019)
    Objectives: Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016. Methods: Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory. Results: A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus-positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton-Valentine leucocidin (PVL)-positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p Conclusions: Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host. (c) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
  • Rossow, H.; Ollgren, J.; Hytonen, J.; Rissanen, H.; Huitu, O.; Henttonen, H.; Kuusi, M.; Vapalahti, O. (2015)
    We studied the incidence of reported tularaemia by year and region and the prevalence of antibodies against Francisella tularensis in the adult general population in Finland. Moreover, we assessed the correlation between vole population cycles and human tularaemia outbreaks. The seroprevalence study made use of serum samples from a nationwide population-based health survey (Health 2000). The samples of 1,045 randomly selected persons, representative for the Finnish population in each region, were screened with an enzyme-linked immunosorbent assay (ELISA) for the presence of IgG antibodies against F. tularensis, and positive results were further confirmed by immunoblotting. A serological response to F. tularensis was found in 2% (95% confidence interval: 1.1-3.5) of the population. Incidence and seroprevalence were highest in the same areas, and vole population peaks clearly preceded tularaemia outbreaks one year later.
  • Kauppinen, Ari; Siponen, Sallamaari; Pitkänen, Tarja; Holmfeldt, Karin; Pursiainen, Anna; Torvinen, Eila; Miettinen, Ilkka T. (2021)
    Bacteriophage control of harmful or pathogenic bacteria has aroused growing interest, largely due to the rise of antibiotic resistance. The objective of this study was to test phages as potential agents for the biocontrol of an opportunistic pathogen Pseudomonas aeruginosa in water. Two P. aeruginosa bacteriophages (vB_PaeM_V523 and vB_PaeM_V524) were isolated from wastewater and characterized physically and functionally. Genomic and morphological characterization showed that both were myoviruses within the Pbunavirus genus. Both had a similar latent period (50-55 min) and burst size (124-134 PFU/infected cell), whereas there was variation in the host range. In addition to these environmental phages, a commercial Pseudomonas phage, JG003 (DSM 19870), was also used in the biocontrol experiments. The biocontrol potential of the three phages in water was tested separately and together as a cocktail against two P. aeruginosa strains; PAO1 and the environmental strain 17V1507. With PAO1, all phages initially reduced the numbers of the bacterial host, with phage V523 being the most efficient (>2.4 log(10) reduction). For the environmental P. aeruginosa strain (17V1507), only the phage JG003 caused a reduction (1.2 log(10)) compared to the control. The cocktail of three phages showed a slightly higher decrease in the level of the hosts compared to the use of individual phages. Although no synergistic effect was observed in the host reduction with the use of the phage cocktail, the cocktail-treated hosts did not appear to acquire resistance as rapidly as hosts treated with a single phage. The results of this study provide a significant step in the development of bacteriophage preparations for the control of pathogens and harmful microbes in water environments.
  • Seecharran, Tristan; Kalin-Manttari, Laura; Koskela, Katja; Nikkari, Simo; Dickins, Benjamin; Corander, Jukka; Skurnik, Mikael; McNally, Alan (2017)
    Yersinia pseudotuberculosis is a Gram-negative intestinal pathogen of humans and has been responsible for several nationwide gastrointestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic species of the genus Yersinia, Yersinia pestis and Yersinia enterocolitica allowing a high-resolution understanding of the ecology, evolution and dissemination of these pathogens. However, to date no purpose-designed large-scale global population genomic analysis of Y. pseudotuberculosis has been performed. Here we present analyses of the genomes of 134 strains of Y. pseudotuberculosis isolated from around the world, from multiple ecosystems since the 1960s. Our data display a phylogeographic split within the population, with an Asian ancestry and subsequent dispersal of successful clonal lineages into Europe and the rest of the world. These lineages can be differentiated by CRISPR cluster arrays, and we show that the lineages are limited with respect to inter-lineage genetic exchange. This restriction of genetic exchange maintains the discrete lineage structure in the population despite co-existence of lineages for thousands of years in multiple countries. Our data highlights how CRISPR can be informative of the evolutionary trajectory of bacterial lineages, and merits further study across bacteria.
  • Aalto-Araneda, Mariella; Lunden, Janne; Markkula, Annukka; Hakola, Satu; Korkeala, Hannu (2019)
    Listeria monocytogenes causes the foodborne illness listeriosis, which exhibits high fatality among people in risk groups. The incidence of listeriosis has increased in Europe, which raises concerns about L. monocytogenes occurrence in foodstuffs. Ready-to-eat seafood products are considered particularly risky vehicles. Poor hygiene at processing facilities predisposes them to L. monocytogenes contamination, which can be controlled by stringent self-checking system measures. We examined the association of fish-processing plant operational and hygiene practices with the occurrence of L. monocytogenes in vacuum-packaged gravad (cold-salted) and cold-smoked salmon and rainbow trout products. Product sampling of 21 fish-processing plants was carried out, and operational procedures relating to L. monocytogenes control were surveyed using an in-depth risk assessment questionnaire. L. monocytogenes occurred only in sliced and mainly in gravad products of seven fish-processing plants. Shortages in preventive measures were discovered predominantly among the L. monocytogenes positive fish-processing plants. Using generalized linear modeling, we identified the following features associated with L. monocytogenes product contamination: the number of processing machines, deficiencies in the processing environment and machinery sanitation, and staff movement from areas of low toward high hygiene. Furthermore, performing frequent periodic thorough sanitation alongside everyday sanitation practices associated with a decreased risk of product contamination.
  • Wolthers, Katja C.; Susi, Petri; Jochmans, Dirk; Koskinen, Janne; Landt, Olfert; Sanchez, Neus; Palm, Kaia; Neyts, Johan; Butcher, Sarah J. (2019)
    Several research groups in Europe are active on different aspects of human picornavirus research. The AIROPico (Academia-Industry R&D Opportunities for Picornaviruses) consortium combined the disciplines of pathogenesis, diagnostics and therapy development in order to fill the gaps in our understanding of how picornaviruses cause human disease and how to combat them. AIROPico was the first EU consortium dedicated to human picornavirus research and development, and has largely accelerated and improved R&D on picornavirus biology, diagnostics and therapy. In this article, we present the progress on pathogenesis, diagnostics and treatment strategy developments for human picornaviruses resulting from the structured, translational research approach of the AIROPico consortium. We here summarize new insights in protection against infection by maternal or cross-protective antibodies, the visualisation of interactions between virus and neutralizing antibodies by cryoEM structural imaging, and the outcomes from a picornavirus-infected human 3D organoid. Progress in molecular detection and a fast typing assay for rhinovirus species are presented, as well as the identification of new compounds potentially interesting as therapeutic compounds.
  • Mueller, Janis A.; Harms, Mirja; Krueger, Franziska; Gross, Ruediger; Joas, Simone; Hayn, Manuel; Dietz, Andrea N.; Lippold, Sina; von Einem, Jens; Schubert, Axel; Michel, Manuela; Mayer, Benjamin; Cortese, Mirko; Jang, Karen S.; Sandi-Monroy, Nathallie; Deniz, Miriam; Ebner, Florian; Vapalahti, Olli; Otto, Markus; Bartenschlager, Ralf; Herbeuval, Jean-Philippe; Schmidt-Chanasit, Jonas; Roan, Nadia R.; Muench, Jan (2018)
    Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid.
  • Malik, Nayab; Kotecha, Abhay; Gold, Sarah; Asfor, Amin; Ren, Jingshan; Huiskonen, Juha T.; Tuthill, Tobias J.; Fry, Elizabeth E.; Stuart, David I. (2017)
    Foot-and-mouth disease virus (FMDV) belongs to the aphthovirus genus of the Picornaviridae, a family of small, icosahedral, non-enveloped, single-stranded RNA viruses. It is a highly infectious pathogen and is one of the biggest hindrances to the international trade of animals and animal products. FMDV capsids (which are unstable below pH6.5) release their genome into the host cell from an acidic compartment, such as that of an endosome, and in the process dissociate into pentamers. Whilst other members of the family (enteroviruses) have been visualized to form an expanded intermediate capsid with holes from which inner capsid proteins (VP4), N-termini (VP1) and RNA can be released, there has been no visualization of any such state for an aphthovirus, instead the capsid appears to simply dissociate into pentamers. Here we present the 8-angstrom resolution structure of isolated dissociated pentamers of FMDV, lacking VP4. We also found these pentamers to re-associate into a rigid, icosahedrally symmetric assembly, which enabled their structure to be solved at higher resolution (5.2 angstrom). In this assembly, the pentamers unexpectedly associate 'inside out', but still with their exposed hydrophobic edges buried. Stabilizing interactions occur between the HI loop of VP2 and its symmetry related partners at the icosahedral 3-fold axes, and between the BC and EF loops of VP3 with the VP2 beta B-strand and the CD loop at the 2-fold axes. A relatively extensive but subtle structural rearrangement towards the periphery of the dissociated pentamer compared to that in the mature virus provides insight into the mechanism of dissociation of FMDV and the marked difference in antigenicity.