The Experts below are selected from a list of 3105 Experts worldwide ranked by ideXlab platform
Michael G. Rossmann - One of the best experts on this subject based on the ideXlab platform.
-
Sialic acid-dependent cell entry of human Enterovirus D68
Nature Communications, 2015Co-Authors: Ju Sheng, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Frank J. M. Van Kuppeveld, Chuan Xiao, Michael G. RossmannAbstract:Human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other Enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry. The human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory infections, but despite its prevalence the exact mechanism mediating its cell entry have not been fully established. Here, the authors show how EV-D68 binds to sialic acid on the cell surface to initiate infection.
-
sialic acid dependent cell entry of human Enterovirus D68
Nature Communications, 2015Co-Authors: Ju Sheng, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Frank J. M. Van Kuppeveld, Chuan Xiao, Michael G. RossmannAbstract:The human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory infections, but despite its prevalence the exact mechanism mediating its cell entry have not been fully established. Here, the authors show how EV-D68 binds to sialic acid on the cell surface to initiate infection.
-
Sialic acid-dependent cell entry of human Enterovirus D68
Nature communications, 2015Co-Authors: Yue Liu, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Ju Sheng, Chuan Xiao, Frank J. M. Van Kuppeveld, Michael G. RossmannAbstract:Human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the 'canyon' on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other Enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.
Kevin Messacar - One of the best experts on this subject based on the ideXlab platform.
-
Enterovirus D68 Subclade B3 in Children with Acute Flaccid Paralysis in West Africa, 2016.
Emerging infectious diseases, 2020Co-Authors: Amary Fall, Kevin Messacar, Mamadou Malado Jallow, Ousmane Kebe, Davy E. Kiori, Déborah Goudiaby, Ndack Ndiaye, Hamid Harouna, Mohamed DiaAbstract:We tested for Enterovirus D68 in fecal samples collected during June-September 2016 from 567 patients with acute flaccid paralysis in 7 West Africa nations. Children
-
Enterovirus D68 and acute flaccid myelitis evaluating the evidence for causality
Lancet Infectious Diseases, 2018Co-Authors: Kevin Messacar, Edwin J Asturias, Alison M Hixon, Coretta Van Leerbuter, H G M Niesters, Kenneth L Tyler, Mark J AbzugAbstract:Summary Increased circulation of Enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon condition of paralysis due to lesions in the anterior horn of the spinal cord. The identification of Enterovirus D68 in respiratory specimens from cases of acute flaccid myelitis worldwide further supports an association, yet the absence of direct virus isolation from affected tissues, infrequent detection in cerebrospinal fluid, and the absence, until recently, of an animal model has left the causal nature of the relationship unproven. In this Personal View we evaluate epidemiological and biological evidence linking Enterovirus D68 and acute flaccid myelitis. We applied the Bradford Hill criteria to investigate the evidence for a causal relationship and highlight the importance of comprehensive surveillance and research to further characterise the role of Enterovirus D68 in acute flaccid myelitis and pursue effective therapies and prevention strategies.
-
Surveillance for Enterovirus D68 in colorado children reveals continued circulation.
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2017Co-Authors: Kevin Messacar, Christine C. Robinson, Kristin Pretty, Ji Yuan, Samuel R. DominguezAbstract:Abstract Background The largest, most widespread outbreak of Enterovirus D68 respiratory disease occurred from August to December of 2014 in the United States with 1153 confirmed infections in 49 states. The epidemiology of Enterovirus D68 following the 2014 outbreak is unknown. Objectives This study seeks to describe the epidemiology of Enterovirus D68 circulation amongst Colorado children from 2014 to 2016. Study design This is a prospective observational surveillance study of Enterovirus D68 infection amongst children tested for respiratory pathogens from July-October 2014–2016 at Children’s Hospital Colorado (CHCO), a quaternary care children’s hospital in Aurora, CO. Results Amongst rhinovirus/Enterovirus positive respiratory specimens from intensive care unit patients, ninety-eight of 314 (31.2%) in 2014, none of 307 (0%) specimens in 2015, and 19 of 240 (7.9%) specimens in 2016 were identified as Enterovirus D68. Amongst respiratory specimens from all patients during the prospective active surveillance period, none of 1469 (0%) in 2015 and 46 of 1403 (3.3%) were positive for Enterovirus D68. Conclusions Surveillance for Enterovirus D68 amongst respiratory specimens at a quaternary care children’s hospital revealed a seasonal pattern of circulation in the late summer to early fall of 2014 and 2016. Continued surveillance of respiratory specimens is necessary to define the circulation pattern and understand the epidemiology of this emerging pathogen.
-
Enterovirus-D68 in Critically Ill Children: a Comparison with Pandemic H1N1 Influenza
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Car, 2016Co-Authors: Suchitra Rao, Kevin Messacar, Michelle Torok, Anne-marie Rick, Jeffrey Holzberg, Aaron Montano, Dayanand Bagdure, Donna J. Curtis, M. Steven Oberste, W. Allan NixAbstract:OBJECTIVE In 2014, the Unites States experienced an outbreak of Enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from Enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown. DESIGN AND SETTING In this retrospective cohort study, we characterized the clinical features of children with Enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010. PATIENTS PICU patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Ninety-seven severely ill children with Enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with Enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with Enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other Enteroviruses and rhinoviruses, children with Enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both). CONCLUSIONS Critically ill children with Enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the Enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes.
-
The Emergence of Enterovirus-D68.
Microbiology spectrum, 2016Co-Authors: Kevin Messacar, Mark J Abzug, Samuel R. DominguezAbstract:Enterovirus-D68 (EV-D68) is a unique Enterovirus, similar to human rhinoviruses, spread via the respiratory route and primarily causing respiratory disease. Increasing clusters of EV-D68 associated respiratory disease have been reported since 2008, with the largest reported outbreak occurring in North America in 2014. Epidemiologic data and biological plausibility support an association of EV-D68 with the neurologic condition, acute flaccid myelitis. Diagnosis requires EV-D68 specific PCR or viral sequencing of respiratory specimens. Treatment consists of supportive care, as there are no currently available effective vaccines or antiviral therapies. Further research is needed to prepare for future EV-D68 outbreaks of respiratory or neurologic disease.
Peter Simmonds - One of the best experts on this subject based on the ideXlab platform.
-
Increase in Enterovirus D68 Infections in Young Children, United Kingdom, 2006-2016.
Emerging infectious diseases, 2019Co-Authors: Everlyn Kamau, Heli Harvala, Soile Blomqvist, Dung Nguyen, Peter Horby, Richard Pebody, Peter SimmondsAbstract:We determined the change in seroprevalence of Enterovirus D68 (EV-D68) in the United Kingdom in age-stratified cohorts from 2006 to 2016, the period during which EV-D68 emerged as a cause of severe respiratory disease occasionally leading to paralysis. Infections were acquired primarily in infants and young children, and incidence was markedly higher in 2016.
-
Increase in Enterovirus D68 Infections in Young Children, United Kingdom, 2006–2016
Centers for Disease Control and Prevention, 2019Co-Authors: Everlyn Kamau, Heli Harvala, Soile Blomqvist, Dung Nguyen, Peter Horby, Richard Pebody, Peter SimmondsAbstract:We determined the change in seroprevalence of Enterovirus D68 (EV-D68) in the United Kingdom in age-stratified cohorts from 2006 to 2016, the period during which EV-D68 emerged as a cause of severe respiratory disease occasionally leading to paralysis. Infections were acquired primarily in infants and young children, and incidence was markedly higher in 2016
Ju Sheng - One of the best experts on this subject based on the ideXlab platform.
-
Sialic acid-dependent cell entry of human Enterovirus D68
Nature Communications, 2015Co-Authors: Ju Sheng, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Frank J. M. Van Kuppeveld, Chuan Xiao, Michael G. RossmannAbstract:Human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other Enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry. The human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory infections, but despite its prevalence the exact mechanism mediating its cell entry have not been fully established. Here, the authors show how EV-D68 binds to sialic acid on the cell surface to initiate infection.
-
sialic acid dependent cell entry of human Enterovirus D68
Nature Communications, 2015Co-Authors: Ju Sheng, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Frank J. M. Van Kuppeveld, Chuan Xiao, Michael G. RossmannAbstract:The human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory infections, but despite its prevalence the exact mechanism mediating its cell entry have not been fully established. Here, the authors show how EV-D68 binds to sialic acid on the cell surface to initiate infection.
-
Sialic acid-dependent cell entry of human Enterovirus D68
Nature communications, 2015Co-Authors: Yue Liu, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Ju Sheng, Chuan Xiao, Frank J. M. Van Kuppeveld, Michael G. RossmannAbstract:Human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the 'canyon' on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other Enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.
Hendrik Jan Thibaut - One of the best experts on this subject based on the ideXlab platform.
-
Sialic acid-dependent cell entry of human Enterovirus D68
Nature Communications, 2015Co-Authors: Ju Sheng, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Frank J. M. Van Kuppeveld, Chuan Xiao, Michael G. RossmannAbstract:Human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other Enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry. The human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory infections, but despite its prevalence the exact mechanism mediating its cell entry have not been fully established. Here, the authors show how EV-D68 binds to sialic acid on the cell surface to initiate infection.
-
sialic acid dependent cell entry of human Enterovirus D68
Nature Communications, 2015Co-Authors: Ju Sheng, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Frank J. M. Van Kuppeveld, Chuan Xiao, Michael G. RossmannAbstract:The human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory infections, but despite its prevalence the exact mechanism mediating its cell entry have not been fully established. Here, the authors show how EV-D68 binds to sialic acid on the cell surface to initiate infection.
-
Sialic acid-dependent cell entry of human Enterovirus D68
Nature communications, 2015Co-Authors: Yue Liu, Geng Meng, Hendrik Jan Thibaut, Jim Baggen, Ju Sheng, Chuan Xiao, Frank J. M. Van Kuppeveld, Michael G. RossmannAbstract:Human Enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the 'canyon' on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other Enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.
-
Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68
Antimicrobial Agents and Chemotherapy, 2015Co-Authors: Adam Meijer, Mathy Froeyen, Hendrik Jan Thibaut, Jim Baggen, Shyla George, John Vernachio, Frank J. M. Van Kuppeveld, Linlin Zhang, Pieter LeyssenAbstract:We investigated the susceptibility of 10 Enterovirus D68 (EV-D68) isolates (belonging to clusters A, B, and C) to (entero)virus inhibitors with different mechanisms of action. The 3C-protease inhibitors proved to be more efficient than enviroxime and pleconaril, which in turn were more effective than vapendavir and pirodavir. Favipiravir proved to be a weak inhibitor. Resistance to pleconaril maps to V69A in the VP1 protein, and resistance to rupintrivir maps to V104I in the 3C protease. A structural explanation of why both substitutions may cause resistance is provided.