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Shamsudeen F. Fagbo Leila Skakni Daniel K.W. Chu Musa A. Garbati Mercy Joseph Malik Peiris Ahmed M. Hakawi 《Emerging infectious diseases》2015,21(11):1981-1988
We investigated an outbreak of Middle East respiratory syndrome (MERS) at King
Fahad Medical City (KFMC), Riyadh, Saudi Arabia, during March 29–May 21,
2014. This outbreak involved 45 patients: 8 infected outside KFMC, 13 long-term
patients at KFMC, 23 health care workers, and 1 who had an indeterminate source
of infection. Sequences of full-length MERS coronavirus (MERS-CoV) from 10
patients and a partial sequence of MERS-CoV from another patient, when compared
with other MERS-CoV sequences, demonstrated that this outbreak was part of a
larger outbreak that affected multiple health care facilities in Riyadh and
possibly arose from a single zoonotic transmission event that occurred in
December 2013 (95% highest posterior density interval November 8,
2013–February 10, 2014). This finding suggested continued health
care–associated transmission for 5 months. Molecular epidemiology
documented multiple external introductions in a seemingly contiguous outbreak
and helped support or refute transmission pathways suspected through
epidemiologic investigation. 相似文献
14.
Wan Beom Park Ranawaka A.P.M. Perera Pyoeng Gyun Choe Eric H.Y. Lau Seong Jin Choi June Young Chun Hong Sang Oh Kyoung-Ho Song Ji Hwan Bang Eu Suk Kim Hong Bin Kim Sang Won Park Nam Joong Kim Leo Lit Man Poon Malik Peiris Myoung-don Oh 《Emerging infectious diseases》2015,21(12):2186-2189
We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease. 相似文献
15.
The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. 相似文献
16.
Ranawaka A. P. M. Perera Ronald Ko Owen T. Y. Tsang David S. C. Hui Mike Y. M. Kwan Christopher J. Brackman Esther M. W. To Hui-ling Yen Kathy Leung Samuel M. S. Cheng Kin Ho Chan Karl C. K. Chan Ka-Chi Li Linda Saif Vanessa R. Barrs Joseph T. Wu Thomas H. C. Sit Leo L. M. Poon Malik Peiris 《Journal of clinical microbiology》2021,59(2)
17.
Arambawatta Kapila Abeysundara Anushka Ihalagedera Dhammika Nawarathna Gayani Nandasena Tharanga Peiris Roshan Banneheka Shyama Nanayakkara Deepthi 《Anatomical science international / Japanese Association of Anatomists》2021,96(4):509-516
Anatomical Science International - Cementoenamel junction is an anatomical landmark which indicates the meeting point of enamel of the crown and the cementum of the root. It is an important... 相似文献
18.
Michael C. W. Chan Denise I. T. Kuok Connie Y. H. Leung Kenrie P. Y. Hui Sophie A. Valkenburg Eric H. Y. Lau John M. Nicholls Xiaohui Fang Yi Guan Jae W. Lee Renee W. Y. Chan Robert G. Webster Michael A. Matthay J. S. Malik Peiris 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(13):3621-3626
Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.Acute lung injury is a continuum of clinical and radiographic changes, terminating at its most severe, with acute respiratory distress syndrome. Infection with highly pathogenic avian influenza (HPAI) viruses of the H5N1 and more recent H7N9 subtypes often leads to acute lung injury whereas seasonal influenza viruses and the 2009 pandemic H1N1 influenza viruses do so more rarely. The underlying mechanisms of influenza-related acute lung injury remain unclear, and effective therapies are lacking. Viruses that are highly pathogenic to humans (e.g., H5N1 viruses) may differ intrinsically from the less pathogenic (LP) (e.g., seasonal H1N1) viruses in their replication competence, cell tropism, and/or cytokine dysregulation (1, 2). Early treatment of H5N1 disease with the antiinfluenza drug oseltamivir is helpful but does not ensure a favorable outcome (3). Thus, effective adjunctive therapies that do not compromise beneficial host defenses are needed (4).H5N1 (5) and H7N9 (6) influenza viruses target alveolar epithelial cells, which form the crucial gas exchange interface in the lung. These cells also help to maintain intraalveolar and intravascular fluid homeostasis by vectorial transport of sodium, chloride, and water from the apical to the basolateral surface of the alveolar epithelium [alveolar fluid clearance (AFC)]. Impaired AFC and increased alveolar protein permeability (APP) contribute to acute lung injury (7). Therapies that normalize alveolar fluid clearance are likely to be free of off-target effects, unlike immunomodulation, that may promote virus replication.Human bone marrow-derived multipotent mesenchymal stromal cells (MSCs) have applications in multiple clinical disorders, including sepsis, myocardial infarction, diabetes, and acute renal failure (8). Allogeneic MSC therapy has beneficial preclinical effects on endotoxin-, bacteria-, and ventilator-induced acute lung injury (9) via MSC secretion of the soluble paracrine growth factors angiopoietin-1 (Ang1) and keratinocyte growth factor (KGF) (9, 10). MSCs can also transfer mitochondria and microvesicles that modulate immunity and epithelial response to injury (11). Current clinical trials are testing MSCs as a therapy for sepsis and acute respiratory distress syndrome (12). However, little is known about the impact of MSCs on acute respiratory viral infections, including influenza, with the exception of a study in which MSCs failed to reduce influenza-induced lung injury in mice (13). Here, we showed that influenza A/H5N1 virus infection dysregulates AFC and APP in vitro by inducing infected cells to release soluble mediators that down-regulate alveolar sodium and chloride transporters. When we cocultured alveolar epithelium with MSCs, these injury mechanisms were prevented or reduced. We then treated mice infected with influenza A/H5N1 with MSCs and demonstrated a clinically significant reduction in lung pathology and increased survival in association with a modulation of these pathogenic mechanisms in vivo. 相似文献
19.
Thomas Haselhorst Ka Tim Choy Hui‐Ling Yen Joseph S. M. Peiris Mark von Itzstein John M. Nicholls 《Influenza and other respiratory viruses》2014,8(2):235-242
Objectives
The main function of influenza neuraminidase (NA) involves enzymatic cleavage of sialic acid from the surface of host cells resulting in the release of the newly produced virions from infected cells, as well as aiding the movement of virions through sialylated mucus present in the respiratory tract. However, there has previously been little information on the binding affinity of different forms of sialylated glycan with NA. Our objectives were then to investigate both sialic acid binding and cleavage of neuraminidase at an atomic resolution level.Design
Nuclear magnetic resonance (NMR) spectroscopy was used to investigate pH and temperature effects on binding and cleavage as well as to interrogate the selectivity of human-like or avian-like receptors for influenza neuraminidase N1 derived from a range of different influenza virus strains including human seasonal H1N1, H1N1pdm09 and avian H5N1.Results
We demonstrated that an acidic pH and physiological temperature are required for efficient NA enzymatic activity; however a change in the pH had a minimum effect on the NA-sialic acid binding affinity. Our data comparing α-2,3- and α-2,6-sialyllactose indicated that the variation in neuraminidase activity on different ligands correlated with a change in binding affinity. Epitope mapping of the sialylglycans interacting with NAs from different viral origin showed different binding profiles suggesting that different binding conformations were adopted.Conclusions
The data presented in this study demonstrated that physicochemical conditions (pH in particular) could affect the NA enzymatic activity with minor effect on ligand binding. NA cleavage specificity seemed to be associated with a difference in binding affinity to different ligands, suggesting a relationship between the two events. These findings have implications regarding the replication cycle of influenza infection in the host where different sialidase activities would influence penetration through the respiratory mucin barrier and the release of the newly generated virus from the infected cells. 相似文献20.
Peiris AN Bailey BA Grant WB Mascitelli L 《Lancet》2012,379(9827):1699; author reply 1700-1699; author reply 1701