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43 results on '"Groppelli, Elisabetta"'

3. Implications of O-glycan modifications in the hinge region of a plant-produced SARS-CoV-2-IgA antibody on functionality

Author

Uetz, Pia, primary, Göritzer, Kathrin, additional, Vergara, Emil, additional, Melnik, Stanislav, additional, Grünwald-Gruber, Clemens, additional, Figl, Rudolf, additional, Deghmane, Ala-Eddine, additional, Groppelli, Elisabetta, additional, Reljic, Rajko, additional, Ma, Julian K.-C., additional, Stöger, Eva, additional, and Strasser, Richard, additional

Published
2024
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4. Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection

Author

Zhang, Changwang, Zhou, Shi, Groppelli, Elisabetta, Pellegrino, Pierre, Williams, Ian, Borrow, Persephone, Chain, Benjamin M., and Jolly, Clare

Subjects
Quantitative Biology - Populations and Evolution, Computer Science - Artificial Intelligence, Computer Science - Computational Engineering, Finance, and Science, Physics - Biological Physics, Quantitative Biology - Cell Behavior
Abstract

HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts. The contribution of this hybrid spreading mechanism, which is also a characteristic of some important computer worm outbreaks, to HIV-1 progression in vivo remains unknown. Here we present a new mathematical model that explicitly incorporates the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the consequences for HIV-1 pathogenenesis. The model captures the major phases of the HIV-1 infection course of a cohort of treatment naive patients and also accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading is critical to seed and establish infection, and that cell-to-cell spread and increased CD4+ T cell activation are important for HIV-1 progression. Notably, the model predicts that cell-to-cell spread becomes increasingly effective as infection progresses and thus may present a considerable treatment barrier. Deriving predictions of various treatments' influence on HIV-1 progression highlights the importance of earlier intervention and suggests that treatments effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS. This study suggests that hybrid spreading is a fundamental feature of HIV infection, and provides the mathematical framework incorporating this feature with which to evaluate future therapeutic strategies.

Published
2015
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5. Functional analyses of novel insect virus IRES elements

Author

Groppelli, Elisabetta

Subjects
579.2
Abstract

Rhopalosiphum padi virus (RhPV) is a member of the Dicistroviridae. The genomes of these viruses contain two open reading frames, each preceded by distinct internal ribosome entry site (IRES) elements. The activity of the RhPV 5' IRES element has previously been demonstrated in mammalian, insect and plant translation systems. It has also been shown that the RhPV 5' IRES forms 48S initiation complexes in vitro with just the mammalian initiation factors eIF2, eIF3 and elFl. It is also possible to delete large regions of the 5' IRES without affecting initiation complex formation. We have now defined the minimal sequences required for directing internal initiation in mammalian, plant and insect translation systems. Fragments of around 130 nt from the 3' portion of the 5'untranslated region (UTR) can direct translation in each of these systems. Thus, the 3' region within the 5'UTR seems to be critical for IRES function. Interestingly, this region is mainly unstructured, making the RhPV 5'IRES unique among viral IRES elements. The RhPV IRES was also compared to the 5'UTR of the insect iflavirus Kakugo virus (KV). Iflaviruses had been initially classified as insect picoma-like viruses alongside the Dicistroviridae. The KV 5'UTR was shown to contain an IRES element similar in function to that of RhPV. Since IRES elements have been shown to require trans-acting factors (ITAFs) for their activity, in addition to the canonical initiation factors, we investigated the interactions of the RhPV IRES with cellular proteins of mammalian, plant and insect origin. In our preliminary studies we identified proteins with a potential role as ITAFs. The potential advantages of the RhPV IRES in biotechnology were assessed in conjunction with a Sindbis virus-based expression system. Like the RhPV 5'IRES, this system is able to function in mammalian and insect systems. However, our preliminary experiments in mammalian cells were not able to clearly establish the advantages of the RhPV 5'IRES in such a system.

Published
2007

6. The QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay for rapid detection of COVID-19 at point-of-care: preliminary evaluation of a novel technology

Author

Caffry, Jessica, primary, Selby, Matthew, additional, Barr, Katie, additional, Morgan, George, additional, McGurk, David, additional, Scully, Philip, additional, Park, Catherine, additional, Caridis, Anna-Maria, additional, Southworth, Emily, additional, Morrison, Jack, additional, Clark, David J., additional, Davies, Benedict M. O., additional, Eckersley, Nicholas M., additional, Groppelli, Elisabetta, additional, Kirwan, Daniela E., additional, Monahan, Irene, additional, Augustin, Yolanda, additional, Toombs, Colin, additional, Planche, Tim, additional, Staines, Henry M., additional, and Krishna, Sanjeev, additional

Published
2023
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7. Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation

Author

Pallett, Scott J. C., primary, Heskin, Joseph, additional, Keating, Fergus, additional, Mazzella, Andrea, additional, Taylor, Hannah, additional, Patel, Aatish, additional, Lamb, Georgia, additional, Sturdy, Deborah, additional, Eisler, Natalie, additional, Denny, Sarah, additional, Charani, Esmita, additional, Randell, Paul, additional, Mughal, Nabeela, additional, Parker, Eleanor, additional, de Oliveira, Carolina Rosadas, additional, Rayment, Michael, additional, Jones, Rachael, additional, Tedder, Richard, additional, McClure, Myra, additional, Groppelli, Elisabetta, additional, Davies, Gary W., additional, O’Shea, Matthew K., additional, and Moore, Luke S. P., additional

Published
2023
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8. ReEBOV Antigen Rapid Test kit for point-of-care and laboratory-based testing for Ebola virus disease: a field validation study

Author

Broadhurst, Mara Jana, Kelly, John Daniel, Miller, Ann, Semper, Amanda, Bailey, Daniel, Groppelli, Elisabetta, Simpson, Andrew, Brooks, Tim, Hula, Susan, Nyoni, Wilfred, Sankoh, Alhaji B, Kanu, Santigi, Jalloh, Alhaji, Ton, Quy, Sarchet, Nicholas, George, Peter, Perkins, Mark D, Wonderly, Betsy, Murray, Megan, and Pollock, Nira R

Published
2015
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9. SARS-CoV-2 Vaccine Immunogenicity in Patients with Gastrointestinal Cancer Receiving Systemic Anti-Cancer Therapy

Author

Lau, David K, primary, Aresu, Maria, additional, Planche, Timothy, additional, Tran, Amina, additional, Lazaro-Alcausi, Retchel, additional, Duncan, Julie, additional, Kidd, Shannon, additional, Cromarty, Susan, additional, Begum, Ruwaida, additional, Rana, Isma, additional, Li, Su, additional, Mohamed, Ali Abdulnabi, additional, Monahan, Irene, additional, Clark, David J, additional, Eckersley, Nicholas, additional, Staines, Henry M, additional, Groppelli, Elisabetta, additional, Krishna, Sanjeev, additional, Mayora-Neto, Martin, additional, Temperton, Nigel, additional, Fribbens, Charlotte, additional, Watkins, David, additional, Starling, Naureen, additional, Chau, Ian, additional, Cunningham, David, additional, and Rao, Sheela, additional

Published
2022
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11. Picornaviruses

Author

Tuthill, Tobias J., Groppelli, Elisabetta, Hogle, James M., Rowlands, David J., and Johnson, John E., editor

Published
2010
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14. SARS-CoV-2 Vaccine Immunogenicity in Patients with Gastrointestinal Cancer Receiving Systemic Anti-Cancer Therapy.

Author

Lau, David K, Aresu, Maria, Planche, Timothy, Tran, Amina, Lazaro-Alcausi, Retchel, Duncan, Julie, Kidd, Shannon, Cromarty, Susan, Begum, Ruwaida, Rana, Isma, Li, Su, Mohamed, Ali Abdulnabi, Monahan, Irene, Clark, David J, Eckersley, Nicholas, Staines, Henry M, Groppelli, Elisabetta, Krishna, Sanjeev, Mayora-Neto, Martin, and Temperton, Nigel

Subjects
TUMOR treatment, THERAPEUTIC use of antineoplastic agents, COVID-19, IMMUNOGLOBULINS, VACCINES, COVID-19 vaccines, VACCINE immunogenicity, GASTROINTESTINAL tumors, TREATMENT effectiveness, COLORECTAL cancer, DESCRIPTIVE statistics, RESEARCH funding, IMMUNOSUPPRESSIVE agents, LONGITUDINAL method, IMMUNOTHERAPY
Abstract

Introduction Patients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination. Materials and Methods Between September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine. Results All 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39. Conclusion Despite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients' ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses. Clinical Trial Registration Number NCT04427280. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Recombinant neutralizing secretory IgA antibodies for preventing mucosal carriage and transmission of SARS-CoV-2

Author

Göritzer, Kathrin, primary, Groppelli, Elisabetta, additional, Grünwald-Gruber, Clemens, additional, Figl, Rudolf, additional, Ni, Fengfeng, additional, Hu, Huimin, additional, Li, Yuncheng, additional, Liu, Yalan, additional, Hu, Qinxue, additional, Puligedda, Rama Devudu, additional, Strasser, Richard, additional, Dessain, Scott, additional, and Ma, Julian, additional

Published
2021
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17. Adjunctive viral cell culture supports treatment decision‐making in patients with secondary humoral immunodeficiency and persistent SARS‐CoV‐2 infection

Author

Pallett, Scott J. C., primary, Wake, Rachel, additional, Youngs, Jonathan, additional, Pope, Cassie, additional, Tan, Ngee Keong, additional, Taylor, Joshua, additional, Hawkins, Lois, additional, Witney, Adam A., additional, Laing, Kenneth G., additional, Monahan, Irene M., additional, Akay, Melek, additional, Cox, Alison, additional, Groppelli, Elisabetta, additional, Kelleher, Peter, additional, Miller, Paul, additional, and Bicanic, Tihana, additional

Published
2021
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18. Accuracy of the Mologic COVID-19 rapid antigen test: a prospective multi-centre analytical and clinical evaluation

Author

CubasAtienzar, Ana, Bell, Fiona, Byrne, Rachel, Buist, Kate, Clark, David J., Cocozza, Michael, Collins, Andrea, Cuevas, Luis, Duvoix, Annelyse, Easom, Nicholas, Edwards, Thomas, Ferreira, Daniela, Fletcher, Tom, Groppelli, Elisabetta, Hyder-Wright, Angela, Kadamus, Ewelina, Kirwan, Daniela E., Kontogianni, Konstantina, Krishna, Sanjeev, Kluczna, Diana, Mark, Julian, Mensah-Kane, Josephine, Miller, Elisha, Mitsi, Elena, Norton, Donna, O'Connor, Emma, Owen, Sophie, Planche, Tim, Shelley, Samuel, Staines, Henry M., Tate, David, Thompson, Caitlin, Walker, Gemma, Williams, Chris, Wooding, Dominic, Fitchett, Joseph R. A., and Adams, Emily

Subjects
qy_4, wc_506
Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the reliance on antigen detection rapid diagnostic tests (Ag-RDTs). Their evaluation at point of use is a priority.\ud \ud Methods: Here, we report a multi-centre evaluation of the analytical sensitivity, specificity, and clinical accuracy of the Mologic COVID-19 Ag-RDT by comparing to reverse transcriptase polymerase chain reaction (RT-qPCR) results from individuals with and without COVID-19 symptoms. Participants had attended hospitals in Merseyside, hospital and ambulance services in Yorkshire, and drive-through testing facilities in Northumberland, UK.\ud \ud Results: The limit of detection of the Mologic COVID-19 Ag-RDT was 5.0 x 102 pfu/ml in swab matrix with no cross-reactivity and interference for any other pathogens tested. A total of 347 participants were enrolled from 26th of November 2020 to 15th of February 2021 with 39.2% (CI 34.0-44.6) testing RT-qPCR positive for SARS-CoV-2. The overall sensitivity and specificity of the Mologic Ag-RDT compared to the reference SARS-CoV-2 RT-qPCR were 85.0% (95% CI 78.3-90.2) and 97.8% (95.0-99.3), respectively. Sensitivity was stratified by RT-qPCR cycle threshold (Ct) and 98.4% (91.3-100) of samples with a Ct less than 20 and 93.2% (86.5-97.2) of samples with a Ct less than 25 were detected using the Ag-RDT. Clinical accuracy was stratified by sampling strategy, swab type and clinical presentation. Mologic COVID-19 Ag-RDT demonstrated highest sensitivity with nose/throat swabs compared with throat or nose swabs alone; however, the differences were not statistically significant.\ud \ud Conclusions: Overall, the Mologic test had high diagnostic accuracy across multiple different settings, different demographics, and on self-collected swab specimens. These findings suggest the Mologic rapid antigen test may be deployed effectively across a range of use settings.

Published
2021

19. The QuantuMDx Q-POC™ SARS-CoV-2 RT-PCR assay for rapid detection of COVID-19 at point-of-care: preliminary evaluation of a novel technology

Author

Caffry, Jessica, primary, Selby, Matthew, additional, Barr, Katie, additional, Morgan, George, additional, McGurk, David, additional, Scully, Philip, additional, Park, Catherine, additional, Caridis, Anna-Maria, additional, Southworth, Emily, additional, Morrison, Jack, additional, Clark, David J, additional, Eckersely, Nickolas, additional, Groppelli, Elisabetta, additional, Kirwan, Daniela E., additional, Monahan, Irene, additional, Augustin, Yolanda, additional, Toombs, Colin, additional, Planche, Tim, additional, Staines, Henry M, additional, and Krishna, Sanjeev, additional

Published
2021
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20. Accuracy of the Mologic COVID-19 rapid antigen test: a prospective multi-centre analytical and clinical evaluation

Author

Cubas-Atienzar, Ana I, primary, Bell, Fiona, additional, Byrne, Rachel L., additional, Buist, Kate, additional, Clark, David J., additional, Cocozza, Michael, additional, Collins, Andrea M., additional, Cuevas, Luis E., additional, Duvoix, Annelyse, additional, Easom, Nicholas, additional, Edwards, Thomas, additional, Ferreira, Daniella M., additional, Fletcher, Tom, additional, Groppelli, Elisabetta, additional, Hyder-Wright, Angela, additional, Kadamus, Ewelina, additional, Kirwan, Daniela E., additional, Kontogianni, Konstantina, additional, Krishna, Sanjeev, additional, Kluczna, Diana, additional, Mark, Julian, additional, Mensah-Kane, Josephine, additional, Miller, Elisha, additional, Mitsi, Elena, additional, Norton, Donna, additional, O'Connor, Emma, additional, Owen, Sophie I., additional, Planche, Tim, additional, Shelley, Samuel, additional, Staines, Henry M., additional, Tate, David, additional, Thompson, Caitlin R., additional, Walker, Gemma, additional, Williams, Christopher T., additional, Wooding, Dominic, additional, Fitchett, Joseph R. A., additional, and Adams, Emily R., additional

Published
2021
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21. Adjunctive viral cell culture supports treatment decision‐making in patients with secondary humoral immunodeficiency and persistent SARS‐CoV‐2 infection.

Author

Pallett, Scott J. C., Wake, Rachel, Youngs, Jonathan, Pope, Cassie, Tan, Ngee Keong, Taylor, Joshua, Hawkins, Lois, Witney, Adam A., Laing, Kenneth G., Monahan, Irene M., Akay, Melek, Cox, Alison, Groppelli, Elisabetta, Kelleher, Peter, Miller, Paul, and Bicanic, Tihana

Subjects
IMMUNE reconstitution inflammatory syndrome, CELL culture, SARS-CoV-2
Abstract

Immunodeficient patients with persistent SARS-CoV-2 infection several months after initial infection may harbour potential for onward transmission of replication-competent virus. Adjunctive viral cell culture supports treatment decision-making in patients with secondary humoral immunodeficiency and persistent SARS-CoV-2 infection Keywords: COVID-19; SARS-CoV-2; recurrence; lymphoma; immune reconstitution EN COVID-19 SARS-CoV-2 recurrence lymphoma immune reconstitution 1170 1174 5 02/28/22 20220301 NES 220301 Persistent Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) infection is observed among patients with haematological malignancy, conferring an increased mortality risk.1,2 Persistent SARS-CoV-2 RNA detection from clinical samples may represent redundant fragmented RNA, replication-competent virus, or reinfection.3,4 Given the role of the host immune response in viral clearance and COVID-19 immunopathogenesis,5,6 distinguishing these scenarios is important for therapeutic decision-making (antiviral I versus i immunomodulatory) as well as preventing onward hospital transmission. Investigation The patient was investigated for persisting SARS-CoV-2 infection/reinfection following relapsing symptomatic pneumonitis associated with positive RNA-polymerase chain reaction (PCR) testing after second-round chemotherapy. [Extracted from the article]

Published
2022
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25. Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases

Author

Arias, Armando, primary, Watson, Simon J., additional, Asogun, Danny, additional, Tobin, Ekaete Alice, additional, Lu, Jia, additional, Phan, My V. T., additional, Jah, Umaru, additional, Wadoum, Raoul Emeric Guetiya, additional, Meredith, Luke, additional, Thorne, Lucy, additional, Caddy, Sarah, additional, Tarawalie, Alimamy, additional, Langat, Pinky, additional, Dudas, Gytis, additional, Faria, Nuno R., additional, Dellicour, Simon, additional, Kamara, Abdul, additional, Kargbo, Brima, additional, Kamara, Brima Osaio, additional, Gevao, Sahr, additional, Cooper, Daniel, additional, Newport, Matthew, additional, Horby, Peter, additional, Dunning, Jake, additional, Sahr, Foday, additional, Brooks, Tim, additional, Simpson, Andrew J.H., additional, Groppelli, Elisabetta, additional, Liu, Guoying, additional, Mulakken, Nisha, additional, Rhodes, Kate, additional, Akpablie, James, additional, Yoti, Zabulon, additional, Lamunu, Margaret, additional, Vitto, Esther, additional, Otim, Patrick, additional, Owilli, Collins, additional, Boateng, Isaac, additional, Okoror, Lawrence, additional, Omomoh, Emmanuel, additional, Oyakhilome, Jennifer, additional, Omiunu, Racheal, additional, Yemisis, Ighodalo, additional, Adomeh, Donatus, additional, Ehikhiametalor, Solomon, additional, Akhilomen, Patience, additional, Aire, Chris, additional, Kurth, Andreas, additional, Cook, Nicola, additional, Baumann, Jan, additional, Gabriel, Martin, additional, Wölfel, Roman, additional, Di Caro, Antonino, additional, Carroll, Miles W., additional, Günther, Stephan, additional, Redd, John, additional, Naidoo, Dhamari, additional, Pybus, Oliver G., additional, Rambaut, Andrew, additional, Kellam, Paul, additional, Goodfellow, Ian, additional, and Cotten, Matthew, additional

Published
2016
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27. Field Laboratory Evaluation of the GeneXpert Ebola Assay for Diagnosis of Ebola Virus Disease in Sierra Leone

Author

Semper, Amanda, primary, Broadhurst, M. Jana, additional, Richards, Jade, additional, Foster, Geraldine M., additional, Simpson, Andrew, additional, Groppelli, Elisabetta, additional, Johnson, Julie, additional, Kelly, J. Dan, additional, Brooks, Tim, additional, Logue, Christopher H., additional, Miller, Ann, additional, Murray, Megan, additional, and Pollock, Nira R., additional

Published
2015
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31. Functional Analyses of Novel Insect Virus IRES Elements

Author

Groppelli, Elisabetta.

Subjects
fungi
Abstract

Rhopalosiphum padi virus (RhPV) is a member of the Dicistroviridae. The genomes of these viruses contain two open reading frames, each preceded by distinct internal ribosome entry site (IRES) elements. The activity of the RhPV 5' IRES element has previously been demonstrated in mammalian, insect and plant translation systems. It has also been shown that the RhPV 5' IRES forms 48S initiation complexes in vitro with just the mammalian initiation factors eIF2, eIF3 and elFl. It is also possible to delete large regions of the 5' IRES without affecting initiation complex formation. We have now defined the minimal sequences required for directing internal initiation in mammalian, plant and insect translation systems. Fragments of around 130 nt from the 3' portion of the 5'untranslated region (UTR) can direct translation in each of these systems. Thus, the 3' region within the 5'UTR seems to be critical for IRES function. Interestingly, this region is mainly unstructured, making the RhPV 5'IRES unique among viral IRES elements. The RhPV IRES was also compared to the 5'UTR of the insect iflavirus Kakugo virus (KV). Iflaviruses had been initially classified as insect picoma-like viruses alongside the Dicistroviridae. The KV 5'UTR was shown to contain an IRES element similar in function to that of RhPV. Since IRES elements have been shown to require trans-acting factors (ITAFs) for their activity, in addition to the canonical initiation factors, we investigated the interactions of the RhPV IRES with cellular proteins of mammalian, plant and insect origin. In our preliminary studies we identified proteins with a potential role as ITAFs. The potential advantages of the RhPV IRES in biotechnology were assessed in conjunction with a Sindbis virus-based expression system. Like the RhPV 5'IRES, this system is able to function in mammalian and insect systems. However, our preliminary experiments in mammalian cells were not able to clearly establish the advantages of the RhPV 5'IRES in such a system.

Published
2007

33. Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors

Author

Wei, Bin, primary, Han, Lei, additional, Abbink, Truus E M, additional, Groppelli, Elisabetta, additional, Lim, Daina, additional, Thaker, Youg Raj, additional, Gao, Wei, additional, Zhai, Rongrong, additional, Wang, Jianhua, additional, Lever, Andrew, additional, Jolly, Clare, additional, Wang, Hongyan, additional, and Rudd, Christopher E, additional

Published
2013
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41. Picornavirus RNA is protected from cleavage by ribonuclease during virion uncoating and transfer across cellular and model membranes

Author

Groppelli, Elisabetta, Levy, Hazel C., Sun, Eileen, Strauss, Mike, Nicol, Clare, Gold, Sarah, Zhuang, Xiaowei, Tuthill, Tobias J., Hogle, James M., and Rowlands, David J.

Subjects
Biology and life sciences, Biochemistry, Proteins, DNA-binding proteins, Nucleases, Ribonucleases, Biology and Life Sciences, Enzymology, Enzymes, Hydrolases, Organisms, Viruses, RNA viruses, Cell Biology, Cellular Structures and Organelles, Vesicles, Liposomes, Extraction techniques, RNA extraction, Cytoplasm, Imaging Techniques, Fluorescence Imaging, Signal Transduction, Cell Signaling, Membrane Receptor Signaling
Abstract

Picornaviruses are non-enveloped RNA viruses that enter cells via receptor-mediated endocytosis. Because they lack an envelope, picornaviruses face the challenge of delivering their RNA genomes across the membrane of the endocytic vesicle into the cytoplasm to initiate infection. Currently, the mechanism of genome release and translocation across membranes remains poorly understood. Within the enterovirus genus, poliovirus, rhinovirus 2, and rhinovirus 16 have been proposed to release their genomes across intact endosomal membranes through virally induced pores, whereas one study has proposed that rhinovirus 14 releases its RNA following disruption of endosomal membranes. For the more distantly related aphthovirus genus (e.g. foot-and-mouth disease viruses and equine rhinitis A virus) acidification of endosomes results in the disassembly of the virion into pentamers and in the release of the viral RNA into the lumen of the endosome, but no details have been elucidated as how the RNA crosses the vesicle membrane. However, more recent studies suggest aphthovirus RNA is released from intact particles and the dissociation to pentamers may be a late event. In this study we have investigated the RNase A sensitivity of genome translocation of poliovirus using a receptor-decorated-liposome model and the sensitivity of infection of poliovirus and equine-rhinitis A virus to co-internalized RNase A. We show that poliovirus genome translocation is insensitive to RNase A and results in little or no release into the medium in the liposome model. We also show that infectivity is not reduced by co-internalized RNase A for poliovirus and equine rhinitis A virus. Additionally, we show that all poliovirus genomes that are internalized into cells, not just those resulting in infection, are protected from RNase A. These results support a finely coordinated, directional model of viral RNA delivery that involves viral proteins and cellular membranes.

Published
2017
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42. Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors.

Author

Bin Wei, Lei Han, Abbink, Truus E. M., Groppelli, Elisabetta, Lim, Daina, Thaker, Youg Raj, Wei Gao, Rongrong Zhai, Jianhua Wang, Lever, Andrew, Jolly, Clare, Hongyan Wang, and Rudd, Christopher E.

Abstract

Background: Immune cell adaptor protein ADAP (adhesion and degranulation-promoting adaptor protein) mediates aspects of T-cell adhesion and proliferation. Despite this, a connection between ADAP and infection by the HIV-1 (human immunodeficiency virus-1) has not been explored. Results: In this paper, we show for the first time that ADAP and its binding to SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) regulate HIV-1 infection via two distinct mechanisms and co-receptors. siRNA downregulation of ADAP, or expression of a mutant that is defective in associating to its binding partner SLP-76 (termed M12), inhibited the propagation of HIV-1 in T-cell lines and primary human T-cells. In one step, ADAP and its binding to SLP-76 were needed for the activation of NF-κB and its transcription of the HIV-1 long terminal repeat (LTR) in cooperation with ligation of co-receptor CD28, but not LFA-1. In a second step, the ADAP-SLP-76 module cooperated with LFA-1 to regulate conjugate formation between T-cells and dendritic cells or other T-cells as well as the development of the virological synapse (VS) and viral spread between immune cells. Conclusions: These findings indicate that ADAP regulates two steps of HIV-1 infection cooperatively with two distinct receptors, and as such, serves as a new potential target in the blockade of HIV-1 infection. [ABSTRACT FROM AUTHOR]

Published
2013
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43. Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases

Author

Arias, Armando, Watson, Simon J, Asogun, Danny, Tobin, Ekaete Alice, Lu, Jia, Phan, My VT, Jah, Umaru, Wadoum, Raoul Emeric Guetiya, Meredith, Luke, Thorne, Lucy, Caddy, Sarah, Tarawalie, Alimamy, Langat, Pinky, Dudas, Gytis, Faria, Nuno R, Dellicour, Simon, Kamara, Abdul, Kargbo, Brima, Kamara, Brima Osaio, Gevao, Sahr, Cooper, Daniel, Newport, Matthew, Horby, Peter, Dunning, Jake, Sahr, Foday, Brooks, Tim, Simpson, Andrew JH, Groppelli, Elisabetta, Liu, Guoying, Mulakken, Nisha, Rhodes, Kate, Akpablie, James, Yoti, Zabulon, Lamunu, Margaret, Vitto, Esther, Otim, Patrick, Owilli, Collins, Boateng, Isaac, Okoror, Lawrence, Omomoh, Emmanuel, Oyakhilome, Jennifer, Omiunu, Racheal, Yemisis, Ighodalo, Adomeh, Donatus, Ehikhiametalor, Solomon, Akhilomen, Patience, Aire, Chris, Kurth, Andreas, Cook, Nicola, Baumann, Jan, Gabriel, Martin, Wölfel, Roman, Di Caro, Antonino, Carroll, Miles W, Günther, Stephan, Redd, John, Naidoo, Dhamari, Pybus, Oliver G, Rambaut, Andrew, Kellam, Paul, Goodfellow, Ian, and Cotten, Matthew

Subjects
Ebola virus, evolution, transmission, outbreak sequencing, 3. Good health
Abstract

To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts.

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