| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 3. |
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| 4. |
- Chase, Christopher C L, et al.
(författare)
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Immune response to bovine viral diarrhea virus--looking at newly defined targets.
- 2015
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Ingår i: Animal Health Research Reviews. - 1466-2523 .- 1475-2654. ; 16:1, s. 4-14
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Tidskriftsartikel (refereegranskat)abstract
- Bovine viral diarrhea virus (BVDV) has long been associated with a wide variety of clinical syndromes and immune dysregulation, many which result in secondary bacterial infections. Current understanding of immune cell interactions that result in activation and tolerance are explored in light of BVDV infection including: depletion of lymphocytes, effects on neutrophils, natural killer cells, and the role of receptors and cytokines. In addition, we review some new information on the effect of BVDV on immune development in the fetal liver, the role of resident macrophages, and greater implications for persistent infection.
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| 5. |
- Darweesh, Mahmoud, et al.
(författare)
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Adenovirus VA RNAI Blocks ASC Oligomerization and Inhibits NLRP3 Inflammasome Activation
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Virus infected immune cells can rapidly respond to the invader by activating the inflammasome and as a consequence release proinflammatory cytokines and eventually die by pyroptosis. In human adenovirus-5 (Ad5) infected THP-1 cells, inhibition of NLRP3 inflammasome activation was demonstrated by a decreased secretion of HMGB1 and matured forms of caspase-1and IL-1ß. An Ad5 mutant virus defective in expression of the non-coding VA RNAI failed to inhibit the NLRP3 inflammasome and in addition displayed formation of ASC specks and increased cell lysis. Importantly, in vitro synthesized VA RNAI was able to inhibit the NLRP3 inflammasome activity in THP-1 cells in the absence of an Ad5 infection, suggesting that VA RNAI binding to PKR and blocking its function is sufficient for inhibition of the NLRP3 inflammasome. Although the inhibition of NLRP3 inflammasome activation required the phylogenetically conserved base paired tetranucleotide sequence in the central stem of VA RNAI, we demonstrate that PKR binding to VA RNAI primarily protected the apical stem, but not the tetranucleotide sequence itself. VA RNAI did not influence the interaction between PKR and NLRP3. In contrast, we describe a novel interaction between PKR and ASC and further show that VA RNAI inhibited ASC phosphorylation and oligomerization. Collectively, our results indicate a novel role for Ad5 VA RNAI as an inhibitor of NLRP3 inflammasome activation by targeting the cellular pro-inflammatory protein PKR.
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| 6. |
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| 7. |
- Darweesh, Mahmoud F, et al.
(författare)
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BVDV Npro protein mediates the BVDV induced immunosuppression through interaction with cellular S100A9 protein.
- 2018
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Ingår i: Microbial Pathogenesis. - : Elsevier BV. - 0882-4010 .- 1096-1208. ; 121, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- The innate immune response is a vital part of the body's antiviral defense system. The innate immune response is initiated by various receptor interactions, including danger associated molecular patterns (DAMPs). The S100A9 is a member of the DAMPs protein family and, is released by activated phagocytic cells such as neutrophils, monocytes, macrophages or endothelial cells, and S100A9 induces its effect through TLR4/MyD88 pathway. Bovine viral diarrhea virus (BVDV) is one of the major devastating disease in the cattle industry worldwide. It shows its effect through immunosuppression and develops persistent infection in calves born from infected cows. The current study revealed that BVDV potentially induced immunosuppression by the interaction of BVDV Npro protein with cellular S100A9 protein. The Inhibition of S100A9 protein expression by small interfering RNA (siRNA) enhanced the virus replication in infected cells. Overexpression of bovine S100A9 enhanced the ncpBVDV2a 1373 mediated Type-I interferon production. A co-immunoprecipitation experiment demonstrated a strong interaction between ncp BVDV2a 1373 Npro protein and cellular S100A9 protein. This suggested that BVDV Npro reduced the S100A9 protein availability/activity in infected cells, resulting in reduced Type-I interferon production. A further study of S100A9-BVDV interaction will be need for better understanding of BVDV pathophysiology.
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| 8. |
- Darweesh, Mahmoud, et al.
(författare)
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ZC3H11A loss of function enhances NF-κB signaling through defective IκBα protein expression
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- ZC3H11A is a cellular protein associated with the transcription export (TREX) complex that is induced during heat-shock. Several nuclear-replicating viruses exploit the mRNA export mechanism of ZC3H11A protein for their efficient replication. Here we show that ZC3H11A protein plays a role in regulation of NF-kappa B signal transduction. Depletion of ZC3H11A resulted in enhanced NF-kappa B mediated signaling, with upregulation of numerous innate immune related mRNAs, including IL-6 and a large group of interferon-stimulated genes. IL-6 upregulation in the absence of the ZC3H11A protein correlated with an increased NF-kappa B transcription factor binding to the IL-6 promoter and decreased IL-6 mRNA decay. The enhanced NF-kappa B signaling pathway in ZC3H11A deficient cells correlated with a defect in I kappa B alpha inhibitory mRNA and protein accumulation. Upon ZC3H11A depletion The I kappa B alpha mRNA was retained in the cell nucleus resulting in failure to maintain normal levels of the cytoplasmic I kappa B alpha mRNA and protein that is essential for its inhibitory feedback loop on NF-kappa B activity. These findings indicate towards a previously unknown mechanism of ZC3H11A in regulating the NF-kappa B pathway at the level of IkB alpha mRNA export.
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| 9. |
- El-Wekil, Mohamed M., et al.
(författare)
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An innovative dual recognition aptasensor for specific detection of Staphylococcus aureus based on Au/Fe3O4 binary hybrid
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic bacteria cause disease outbreaks and threaten human health, prompting the research on advanced detection assays. Herein, we developed a selective molecular imprinted aptasensor for sensitive and prompt quantitation of Staphylococcus aureus (S. aureus) bacteria. The aptasensor was constructed by immobilization of aptamer on gold nanoparticles modified magnetic nanoparticles (apt-AuNPs@ Fe3O4). A functional monomer (o-phenylenediamine, o-phen) was electro-polymerized on the surface of the as-synthesized nanocomposite in the presence of a template (S. aureus). After removing S. aureus, the formed imprinted sites were available to extract pathogenic bacteria from complicated matrices. The surface morphology of the as-fabricated nanocomposites was characterized using different spectroscopic and electrochemical methods. Moreover, we thoroughly evaluated factors affecting the synthesis and determination procedures. The molecular imprinted aptasensor exhibited a wide linear range of 10(1)-10(7) CFU mL(-1) with a Limit of Detection, LOD (signal to noise = 3) of 1 CFU mL(-1). The aptasensor detected S. aureus in milk, conduit water, and apple juice samples with good recoveries % and satisfactory relative standard deviations (RSDs %) values.
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| 10. |
- El-Wekil, Mohamed M., et al.
(författare)
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Enzyme-free and label-free strategy for electrochemical oxaliplatin aptasensing by using rGO/MWCNTs loaded with AuPd nanoparticles as signal probes and electro-catalytic enhancers
- 2020
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Ingår i: Talanta. - : Elsevier BV. - 0039-9140 .- 1873-3573. ; 217
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Tidskriftsartikel (refereegranskat)abstract
- An innovative label free electrochemical aptasensor was developed for the analysis of oxaliplatin (OXAL) for the first time. The DNA oligonucleotide (aptamer) was successfully fabricated, by covalently attaching the amino terminus of the functional DNA on the glassy carbon electrode (GCE) surface modified with reduced graphene oxide (rGO) and multi-walled carbon nanotubes (MWCNTs) loaded with AuPd nanoparticles (AuPd NPs@rGO/MWCNTs/GCE). The stepwise assembly process of aptasensor on AuPd NPs@rGO/MWCNTs/GCE was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The aptamer-OXAL complex formation led to inhibition the electron transfer of Fe(CN)63−/4- on the electrode interface, which was clearly observed by decreasing the peak current of the redox probe. Furthermore, we managed to quantitatively measure OXAL by adding different concentrations of OXAL, while monitoring the decrease of differential pulse voltammogram (DPV) responses of the redox probe. Under the optimized conditions, the electrochemical aptasensor exhibited a linear range of 0.1–170.0 nmol L−1 with LOD of 60.0 pmol L−1. Next, we successfully applied the aptasensor calibrated system to determine OXAL in pharmaceutical injection and human biological samples.
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| 11. |
- Hajikhezri, Zamaneh, et al.
(författare)
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Fragile X-Related Protein FXR1 Controls Human Adenovirus Capsid mRNA Metabolism
- 2023
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 97:2
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Tidskriftsartikel (refereegranskat)abstract
- Human adenoviruses (HAdVs) are widespread pathogens causing a variety of diseases. A well-controlled expression of virus capsid mRNAs originating from the major late transcription unit (MLTU) is essential for forming the infectious virus progeny. However, regulation of the MLTU mRNA metabolism has mainly remained enigmatic. In this study, we show that the cellular RNA-binding protein FXR1 controls the stability of the HAdV-5 MLTU mRNAs, as depletion of FXR1 resulted in increased steady-state levels of MLTU mRNAs. Surprisingly, the lack of FXR1 reduced viral capsid protein accumulation and formation of the infectious virus progeny, indicating an opposing function of FXR1 in HAdV-5 infection. Further, the long FXR1 isoform interfered with MLTU mRNA translation, suggesting FXR1 isoform-specific functions in virus-infected cells. We also show that the FXR1 protein interacts with N6-methyladenosine (m6A)-modified MLTU mRNAs, thereby acting as a novel m6A reader protein in HAdV-5 infected cells. Collectively, our study identifies FXR1 as a regulator of MLTU mRNA metabolism in the lytic HAdV-5 life cycle.
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| 12. |
- Hajikhezri, Zamaneh, et al.
(författare)
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Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections
- 2020
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 12:11
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Forskningsöversikt (refereegranskat)abstract
- The zinc finger proteins make up a significant part of the proteome and perform a huge variety of functions in the cell. The CCCH-type zinc finger proteins have gained attention due to their unusual ability to interact with RNA and thereby control different steps of RNA metabolism. Since virus infections interfere with RNA metabolism, dynamic changes in the CCCH-type zinc finger proteins and virus replication are expected to happen. In the present review, we will discuss how three CCCH-type zinc finger proteins, ZC3H11A, MKRN1, and U2AF1, interfere with human adenovirus replication. We will summarize the functions of these three cellular proteins and focus on their potential pro- or anti-viral activities during a lytic human adenovirus infection.
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| 13. |
- Kases, Katharina, et al.
(författare)
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The RNA-binding protein ZC3H11A interacts with the nuclear poly(A)-binding protein PABPN1 and alters polyadenylation of viral transcripts
- 2023
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Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 299:8
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multiprotein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, NF-kappa B signaling, and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and viral mRNA. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein may act as a novel regulator of polyadenylation of nuclear mRNA.
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| 14. |
- Momin, Tooba, et al.
(författare)
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ZFP36 ring finger protein like 1 significantly suppresses human coronavirus OC43 replication
- 2023
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Ingår i: PeerJ. - : PEERJ INC. - 2167-8359. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- CCCH-type zinc figure proteins (ZFP) are small cellular proteins that are structurally maintained by zinc ions. Zinc ions coordinate the protein structure in a tetrahedral geometry by binding to cystine-cystine or cysteines-histidine amino acids. ZFP's unique structure enables it to interact with a wide variety of molecules including RNA; thus, ZFP modulates several cellular processes including the host immune response and virus replication. CCCH-type ZFPs have shown their antiviral efficacy against several DNA and RNA viruses. However, their role in the human coronavirus is little explored. We hypothesized that ZFP36L1 also suppresses the human coronavirus. To test our hypothesis, we used OC43 human coronavirus (HCoV) strain in our study. We overexpressed and knockdown ZFP36L1 in HCT-8 cells using lentivirus transduction. Wild type, ZFP36L1 overexpressed, and ZFP36L1 knockdown cells were each infected with HCoV-OC43, and the virus titer in each cell line was measured over 96 hours post-infection (p.i.). Our results show that HCoV-OC43 replication was significantly reduced with ZFP36L1 overexpression while ZFP36L1 knockdown significantly enhanced virus replication. ZFP36L1 knockdown HCT-8 cells started producing infectious virus at 48 hours p.i. which was an earlier timepoint as compared to wild-type and ZFP36L1 overexpressed cells. Wild-type and ZFP36L1 overexpressed HCT-8 cells started producing infectious virus at 72 hours p.i. Overall, the current study showed that overexpression of ZFP36L1 suppressed human coronavirus (OC43) production.
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| 15. |
- Punga, Tanel, PhD, 1974-, et al.
(författare)
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Synthesis, Structure, and Function of Human Adenovirus Small Non-Coding RNAs
- 2020
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:10
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Forskningsöversikt (refereegranskat)abstract
- Human adenoviruses (HAdVs) are common pathogens causing a variety of respiratory, ocular and gastrointestinal diseases. To accomplish their efficient replication, HAdVs take an advantage of viral small non-coding RNAs (sncRNAs), which have multiple roles during the virus lifecycle. Three of the best-characterized HAdV sncRNAs; VA RNA, mivaRNA and MLP-TSS-sRNA will be discussed in the present review. Even though VA RNA has been extensively characterized during the last 60 years, this multifunctional molecule continues to surprise us as more of its structural secrets unfold. Likely, the recent developments on mivaRNA and MLP-TSS-sRNA synthesis and function highlight the importance of these sncRNA in virus replication. Collectively, we will summarize the old and new knowledge about these three viral sncRNAs with focus on their synthesis, structure and functions.
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| 16. |
- Rajput, Mrigendra K S, et al.
(författare)
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Both cytopathic and non-cytopathic bovine viral diarrhea virus (BVDV) induced autophagy at a similar rate.
- 2017
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Ingår i: Veterinary Immunology and Immunopathology. - : Elsevier BV. - 0165-2427 .- 1873-2534. ; 193-194, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy is a cellular process that maintains cellular homeostasis by the proteolytic recycling of cytoplasm. Autophagy occurs at basal levels in almost all cells. It is upregulated in cellular stress including starvation, oxidative stress or during infection. Several viruses including flavivirus have developed strategies to subvert or use autophagy for their efficient replication. Bovine viral diarrhea virus (BVDV) is a member of the Flaviviridae family and the pestivirus virus group. BVDV is responsible for significant economic loss in cattle industry worldwide. A unique characteristic of BVDV is the well-characterized genetic changes that can result in two different phenotypes (biotypes) in cell culture: cytopathic (cp) or non-cytopathic (ncp) effects. The ncp viruses are the most prevalent and important for clinical disease. This study was carried out to determine the effect of different BVDV phenotypes using the virus pair, cp TGAC and ncp TGAN in autophagy induction, as well as to investigate the role of autophagy in BVDV induced cytopathic effect.RESULTS: showed that both biotypes (cp and ncp) of BVDV induced autophagy in immortal Madin-Darby bovine kidney (MDBK) cell line as well as primary bovine turbinate (Bt) cells following infection. There was no significant difference between cp or ncp strains of BVDV in autophagosome formation (p<0.05) in either MDBK or Bt cells. The autophagy inhibiting drug, 3-methyladenine (3MA) significantly reduced autophagy (p<0.05) as well as viral replication. While autophagy inducing drug rapamycin significantly enhanced autophagy as well as viral replication. The co-localization study using, BVDV NS5A, Erns and E1 proteins with autophagy marker, light chain-3 (LC3) revealed that BVDV replication was associated with autophagosomes. This study revealed that both cp and ncp strains of BVDV induced autophagy at similar level and used autophagy machinery for their replication.
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| 17. |
- Rajput, Mrigendra K S, et al.
(författare)
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The effect of bovine viral diarrhea virus (BVDV) strains on bovine monocyte-derived dendritic cells (Mo-DC) phenotype and capacity to produce BVDV.
- 2014
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Ingår i: Virology Journal. - 1743-422X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dendritic cells (DC) are important antigen presentation cells that monitor, process, and present antigen to T cells. Viruses that infect DC can have a devastating impact on the immune system. In this study, the ability of bovine viral diarrhea virus (BVDV) to replicate and produce infectious virus in monocyte-derived dendritic cells (Mo-DC) and monocytes was studied. The study also examined the effect of BVDV infection on Mo-DC expression of cell surface markers, including MHCI, MHCII, and CD86, which are critical for DC function in immune response.METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from bovine blood through gradient centrifugation. The adherent monocytes were isolated from PBMCs and differentiated into Mo-DC using bovine recombinant interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GMCSF). To determine the effect of BVDV on Mo-DC, four strains of BVDV were used including the severe acute non-cytopathic (ncp) BVDV2a-1373; moderate acute ncp BVDV2a 28508-5; and a homologous virus pair [i.e., cytopathic (cp) BVDV1b TGAC and ncp BVDV1b TGAN]. The Cooper strain of bovine herpesvirus 1 (BHV1) was used as the control virus. Mo-DC were infected with one of the BVDV strains or BHV-1 and were subsequently examined for virus replication, virus production, and the effect on MHCI, MHCII, and CD86 expression.RESULTS: The ability of monocytes to produce infectious virus reduced as monocytes differentiated to Mo-DC, and was completely lost at 120 hours of maturation. Interestingly, viral RNA increased throughout the course of infection in Mo-DC, and the viral non-structural (NS5A) and envelope (E2) proteins were expressed. The ncp strains of BVDV down-regulated while cp strain up-regulated the expression of the MHCI, MHCII, and CD86 on Mo-DC.CONCLUSIONS: The study revealed that the ability of Mo-DC to produce infectious virus was reduced with its differentiation from monocytes to Mo-DC. The inability to produce infectious virus may be due to a hindrance of virus packaging or release mechanisms. Additionally, the study demonstrated that ncp BVDV down-regulated and cp BVDV up-regulated the expression of Mo-DC cell surface markers MHCI, MHCII, and CD86, which are important in the mounting of immune responses.
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