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https://www.readbyqxmd.com/read/28057259/modified-vaccinia-virus-ankara-history-value-in-basic-research-and-current-perspectives-for-vaccine-development
#1
REVIEW
A Volz, G Sutter
Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment...
2017: Advances in Virus Research
https://www.readbyqxmd.com/read/28050021/systematic-active-surveillance-for-middle-east-respiratory-syndrome-coronavirus-in-camels-in-egypt
#2
Mohamed A Ali, Mahmoud M Shehata, Mokhtar R Gomaa, Ahmed Kandeil, Rabeh El-Shesheny, Ahmed S Kayed, Ahmed N El-Taweel, Mohamed Atea, Nagla Hassan, Ola Bagato, Yassmin Moatasim, Sara H Mahmoud, Omnia Kutkat, Asmaa M Maatouq, Ahmed Osman, Pamela P McKenzie, Richard J Webby, Ghazi Kayali
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%...
January 4, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28049440/an-assessment-of-the-level-of-concern-among-hospital-based-health-care-workers-regarding-mers-outbreaks-in-saudi-arabia
#3
Mostafa A Abolfotouh, Ali A AlQarni, Suliman M Al-Ghamdi, Mahmoud Salam, Mohammed H Al-Assiri, Hanan H Balkhy
BACKGROUND: Middle East Respiratory Syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). More than 80% of reported cases have occurred in Saudi Arabia, with a mortality exceeding 50%. Health-care workers (HCWs) are at risk of acquiring and transmitting this virus, so the concerns of HCWs in Saudi Arabia regarding MERS were evaluated. METHODS: An anonymous, self-administered, previously validated questionnaire was given to 1031 HCWs at three tertiary hospitals in Saudi Arabia from October to December, 2014...
January 3, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28040513/novel-chimeric-virus-like-particles-vaccine-displaying-mers-cov-receptor-binding-domain-induce-specific-humoral-and-cellular-immune-response-in-mice
#4
Chong Wang, Xuexing Zheng, Weiwei Gai, Gary Wong, Hualei Wang, Hongli Jin, Na Feng, Yongkun Zhao, Weijiao Zhang, Nan Li, Guoxing Zhao, Junfu Li, Jinghua Yan, Yuwei Gao, Guixue Hu, Songtao Yang, Xianzhu Xia
Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP)...
December 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/28031370/binding-of-the-methyl-donor-sam-to-mers-cov-2-o-methyltransferase-nsp16-promotes-the-recruitment-of-the-allosteric-activator-nsp10
#5
Wahiba Aouadi, Alexandre Blanjoie, Jean-Jacques Vasseur, Françoise Debart, Bruno Canard, Etienne Decroly
: The Middle East respiratory syndrome coronavirus (MERS-CoV) non-structural protein 16 (nsp16) is an S-adenosyl-L-methionine (SAM)-dependent 2' -O-methyltransferase (MTase) that is thought to methylate the ribose 2' -OH of the first transcribed nucleotide (N1) of viral RNA cap structures. This 2' -O MTase activity is regulated by nsp10. The 2' -O methylation prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated IFIT-1 protein...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28018942/murine-leukemia-virus-mlv-based-coronavirus-spike-pseudotyped-particle-production-and-infection
#6
Jean Kaoru Millet, Gary R Whittaker
Viral pseudotyped particles (pp) are enveloped virus particles, typically derived from retroviruses or rhabdoviruses, that harbor heterologous envelope glycoproteins on their surface and a genome lacking essential genes. These synthetic viral particles are safer surrogates of native viruses and acquire the tropism and host entry pathway characteristics governed by the heterologous envelope glycoprotein used. They have proven to be very useful tools used in research with many applications, such as enabling the study of entry pathways of enveloped viruses and to generate effective gene-delivery vectors...
December 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28009529/high-prevalence-of-middle-east-respiratory-coronavirus-in-young-dromedary-camels-in-jordan
#7
Neeltje van Doremalen, Zaidoun S K Hijazeen, Peter Holloway, Bilal Al Omari, Chester McDowell, Danielle Adney, Hani A Talafha, Javier Guitian, John Steel, Nadim Amarin, Markos Tibbo, Ehab Abu-Basha, Ahmad M Al-Majali, Vincent J Munster, Juergen A Richt
Prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined in 45 dromedary camels from two geographically separated herds in Jordan. Virus shedding was only detected in swabs obtained from the respiratory tract and primarily observed in camels younger than 3 years. MERS-CoV seroprevalence increased with age of camels. Bovine and sheep sera were seronegative. Phylogenetic analysis of partial S2 clustered the Jordanian MERS-CoV strains with contemporary MERS-CoV strains associated with nosocomial outbreaks...
December 23, 2016: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28003490/lineage-a-betacoronavirus-ns2-proteins-and-homologous-torovirus-berne-pp1a-carboxyterminal-domain-are-phosphodiesterases-that-antagonize-activation-of-rnase-l
#8
Stephen A Goldstein, Joshua M Thornbrough, Rong Zhang, Babal K Jha, Yize Li, Ruth Elliott, Katherine Quiroz-Figueroa, Annie I Chen, Robert H Silverman, Susan R Weiss
: Viruses in the family Coronaviridae, with the Nidovirus order, are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory disease in humans. These viruses encode conserved replicase and structural proteins, and more diverse accessory proteins in the 3' end of their genomes that often act as host cell antagonists. We have previously shown that 2', 5' phosphodiesterases (PDE) encoded by the prototypical Betacoronavirus, mouse hepatitis virus (MHV), Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate - ribonuclease L (OAS-RNase L) pathway...
December 21, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27999962/human-lung-ex-vivo-infection-models
#9
REVIEW
Andreas C Hocke, Norbert Suttorp, Stefan Hippenstiel
Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models...
December 20, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27999426/a-camel-derived-mers-cov-with-a-variant-spike-protein-cleavage-site-and-distinct-fusion-activation-properties
#10
Jean Kaoru Millet, Monty E Goldstein, Rachael N Labitt, Hung-Lun Hsu, Susan Daniel, Gary R Whittaker
Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2' fusion activation site-notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1' cleavage site position...
December 21, 2016: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/27989237/modernising-epidemic-science-enabling-patient-centred-research-during-epidemics
#11
EDITORIAL
Amanda M Rojek, Peter W Horby
BACKGROUND: Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers...
December 19, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27966107/the-middle-east-respiratory-syndrome-coronavirus-a-continuing-risk-to-global-health-security
#12
Esam I Azhar, Simone Lanini, Giuseppe Ippolito, Alimuddin Zumla
Two new zoonotic coronaviruses causing disease in humans (Zumla et al. 2015a; Hui and Zumla 2015; Peiris et al. 2003; Yu et al. 2014) have been the focus of international attention for the past 14 years due to their epidemic potential; (1) The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) (Peiris et al. 2003) first discovered in China in 2001 caused a major global epidemic of the Severe Acute Respiratory Syndrome (SARS). (2) The Middle East respiratory syndrome coronavirus (MERS-CoV) is a new corona virus isolated for the first time in a patients who died of severe lower respiratory tract infection in Jeddah (Saudi Arabia) in June 2012 (Zaki et al...
December 14, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27936982/mers-cov-spike-protein-a-key-target-for-antivirals
#13
Lanying Du, Yang Yang, Yusen Zhou, Lu Lu, Fang Li, Shibo Jiang
The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides...
December 21, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27933782/integration-of-global-analyses-of-host-molecular-responses-with-clinical-data-to-evaluate-pathogenesis-and-advance-therapies-for-emerging-and-re-emerging-viral-infections
#14
Shane D Falcinelli, Daniel S Chertow, Jason Kindrachuk
Outbreaks associated with emerging and re-emerging viral pathogens continue to increase in frequency and are associated with an increasing burden to global health. In light of this, there is a need to integrate basic and clinical research for investigating the connections between molecular and clinical pathogenesis and for therapeutic development strategies. Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis...
November 11, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27932291/influenza-not-mers-cov-among-returning-hajj-and-umrah-pilgrims-with-respiratory-illness-kashmir-north-india-2014-15
#15
Parvaiz A Koul, Hyder Mir, Siddhartha Saha, Mandeep S Chadha, Varsha Potdar, Marc-Alain Widdowson, Renu B Lal, Anand Krishnan
BACKGROUND: The increasing reports of Middle East Respiratory Syndrome (MERS) caused by MERS coronavirus (MERS-CoV) from many countries emphasize its importance for international travel. Muslim pilgrimages of Hajj and Umrah involve mass gatherings of international travellers. We set out to assess the presence of influenza and MERS-CoV in Hajj/Umrah returnees with acute respiratory infection. . METHODS: Disembarking passengers (n = 8753) from Saudi Arabia (October 2014 to April 2015) were interviewed for the presence of respiratory symptoms; 977 (11%) reported symptoms and 300 (age 26-90, median 60 years; 140 male) consented to participate in the study...
December 6, 2016: Travel Medicine and Infectious Disease
https://www.readbyqxmd.com/read/27903740/protective-t-cell-responses-featured-by-concordant-recognition-of-middle-east-respiratory-syndrome-coronavirus-derived-cd8-t-cell-epitopes-and-host-mhc
#16
William J Liu, Jiaming Lan, Kefang Liu, Yao Deng, Yanfeng Yao, Shaolian Wu, Hong Chen, Lingling Bao, Haifeng Zhang, Min Zhao, Qihui Wang, Lingxia Han, Yan Chai, Jianxun Qi, Jincun Zhao, Songdong Meng, Chuan Qin, George F Gao, Wenjie Tan
The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity-mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus-infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8(+) T cell epitope drove the conformational fit of Trp(73) on the α1 helix of murine MHC I H-2K(d) In vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27901465/livestock-susceptibility-to-infection-with-middle-east-respiratory-syndrome-coronavirus
#17
Júlia Vergara-Alert, Judith M A van den Brand, W Widagdo, Marta Muñoz, Stalin Raj, Debby Schipper, David Solanes, Ivan Cordón, Albert Bensaid, Bart L Haagmans, Joaquim Segalés
Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs. To determine whether other animals are potential reservoirs, we inoculated MERS-CoV into llamas, pigs, sheep, and horses and collected nasal and rectal swab samples at various times. The presence of MERS-CoV in the nose of pigs and llamas was confirmed by PCR, titration of infectious virus, immunohistochemistry, and in situ hybridization; seroconversion was detected in animals of both species...
February 15, 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/27900364/analysis-of-intrapatient-heterogeneity-uncovers-the-microevolution-of-middle-east-respiratory-syndrome-coronavirus
#18
Donghyun Park, Hee Jae Huh, Yeon Jeong Kim, Dae-Soon Son, Hyo-Jeong Jeon, Eu-Hyun Im, Jong-Won Kim, Nam Yong Lee, Eun-Suk Kang, Cheol In Kang, Doo Ryeon Chung, Jin-Hyun Ahn, Kyong Ran Peck, Sun Shim Choi, Yae-Jean Kim, Chang-Seok Ki, Woong-Yang Park
Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non-consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27894035/an-isothermal-label-free-and-rapid-one-step-rna-amplification-detection-assay-for-diagnosis-of-respiratory-viral-infections
#19
Bonhan Koo, Choong Eun Jin, Tae Yoon Lee, Jeong Hoon Lee, Mi Kyoung Park, Heungsup Sung, Se Yoon Park, Hyun Jung Lee, Sun Mi Kim, Ji Yeun Kim, Sung-Han Kim, Yong Shin
Recently, RNA viral infections caused by respiratory viruses, such as influenza, parainfluenza, respiratory syncytial virus, coronavirus, and Middle East respiratory syndrome-coronavirus (MERS-CoV), and Zika virus, are a major public health threats in the world. Although myriads of diagnostic methods based on RNA amplification have been developed in the last decades, they continue to lack speed, sensitivity, and specificity for clinical use. A rapid and accurate diagnostic method is needed for appropriate control, including isolation and treatment of the patients...
April 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27892925/a-mouse-model-for-mers-coronavirus-induced-acute-respiratory-distress-syndrome
#20
Adam S Cockrell, Boyd L Yount, Trevor Scobey, Kara Jensen, Madeline Douglas, Anne Beall, Xian-Chun Tang, Wayne A Marasco, Mark T Heise, Ralph S Baric
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV...
November 28, 2016: Nature Microbiology
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