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      Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya

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          Abstract

          Background

          Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime.

          Methods

          Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing.

          Results

          HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching.

          Conclusions

          In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.

          Abstract

          Infections with human coronavirus NL63 are common and reinfections occur repeatedly throughout life. A subset of repeat infections show enhanced virus replication with no evidence of genotype switching, indicating that initial exposure is insufficient to elicit a protective immune response.

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          Most cited references26

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          Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

          A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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            Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.

            Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.
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              Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group

              Journal of Virology, 87(14), 7790-7792
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                01 June 2018
                21 March 2018
                21 March 2018
                : 217
                : 11
                : 1728-1739
                Affiliations
                [1 ]Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme
                [2 ]School of Health and Human Sciences, Pwani University, Kilifi, Kenya
                [3 ]Faculty of Infectious and Tropical Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [4 ]Laboratory of Experimental Virology, Academic Medical Center of the University of Amsterdam, the Netherlands
                [5 ]Department of Medicine, Division of Infectious Diseases, Imperial College London
                [6 ]Kymab Ltd., Babraham Research Campus, Cambridge
                [7 ]School of Life Sciences and Zeeman Institute, University of Warwick, Coventry
                [8 ]Wellcome Trust Sanger Institute, Hinxton, United Kingdom
                Author notes

                Current address: Department of Viroscience, Erasmus Medical Center, Rotterdam

                Correspondence: M. Cotten, PhD, Erasmus MC, Wytemaweg 80, 3015CN Rotterdam, Netherlands ( m.cotten@ 123456erasmusmc.nl ).
                Author information
                http://orcid.org/0000-0003-2803-642X
                Article
                jiy098
                10.1093/infdis/jiy098
                6037089
                29741740
                a85d95d3-c514-452f-8ef4-704654e61224
                © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 November 2017
                : 27 February 2018
                Page count
                Pages: 12
                Funding
                Funded by: Wellcome Trust 10.13039/100010269
                Award ID: 102975
                Funded by: Commonwealth Distance Learning Scholarship Scheme
                Award ID: KECD-2013–54
                Funded by: Medical Research Council 10.13039/501100000265
                Award ID: MR/K000551/1
                Award ID: MR/M01360X/1
                Award ID: MR/N010469/1
                Award ID: MC_PC_15103
                Categories
                Major Articles and Brief Reports
                Viruses

                Infectious disease & Microbiology
                virus evolution,coronavirus,repeat infection
                Infectious disease & Microbiology
                virus evolution, coronavirus, repeat infection

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