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      A newly discovered human pneumovirus isolated from young children with respiratory tract disease


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          From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.

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          Fingerprinting genomes using PCR with arbitrary primers.

          Simple and reproducible fingerprints of complex genomes can be generated using single arbitrarily chosen primers and the polymerase chain reaction (PCR). No prior sequence information is required. The method, arbitrarily primed PCR (AP-PCR), involves two cycles of low stringency amplification followed by PCR at higher stringency. We show that strains can be distinguished by comparing polymorphisms in genomic fingerprints. The generality of the method is demonstrated by application to twenty four strains from five species of Staphylococcus, eleven strains of Streptococcus pyogenes and three varieties of Oryza sativa (rice).
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            Respiratory syncytial virus infection: immune response, immunopathogenesis, and treatment.

            Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract infection during infancy and early childhood. Once RSV infection is established, the host immune response includes the production of virus-neutralizing antibodies and T-cell-specific immunity. The humoral immune response normally results in the development of anti-RSV neutralizing-antibody titers, but these are often suboptimal during an infant's initial infection. Even when the production of RSV neutralizing antibody following RSV infection is robust, humoral immunity wanes over time. Reinfection during subsequent seasons is common. The cellular immune response to RSV infection is also important for the clearance of virus. This immune response, vital for host defense against RSV, is also implicated in the immunopathogenesis of severe lower respiratory tract RSV bronchiolitis. Many details of the immunology and immunopathologic mechanisms of RSV disease known at present have been learned from rodent models of RSV disease and are discussed in some detail. In addition, the roles of immunoglobulin E, histamine, and eosinophils in the immunopathogenesis of RSV disease are considered. Although the treatment of RSV bronchiolitis is primarily supportive, the role of ribavirin is briefly discussed. Novel approaches to the development of new antiviral drugs with promising anti-RSV activity in vitro are also described.
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              Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection.

              The decline of maternal respiratory syncytial virus (RSV) specific serum antibodies was studied in 45 children during the first 6 months of life, using a virus neutralization assay and competition ELISAs measuring fusion protein and glycoprotein specific antibodies. In all children RSV neutralizing antibodies were demonstrated at birth, with titers ranging from 33 to 1382. The calculated mean half life of these antibodies was 26 days. Furthermore, in a group of 38 children with suspected RSV infection, all younger than 6 months of age on admission, the diagnostic value of serological assays was evaluated. In 32 children RSV infection was confirmed by virus isolation, direct immune fluorescence and RT-PCR. In 7 patients of this group a significant titer rise in virus neutralization assay was demonstrated. Six additional RSV infected children could be identified by showing the presence of RSV-specific IgM or IgA serum antibodies or by showing an increase in fusion protein or glycoprotein specific antibodies. All serological tests together identified 13 (41%) of the 32 RSV infected patients. It is concluded that in children of this age group, which represent the majority of patients hospitalized with RSV infections, serological assays not only have a limited diagnostic value but are of limited value for sero-epidemiological studies.

                Author and article information

                Nat Med
                Nat. Med
                Nature Medicine
                Nature Publishing Group US (New York )
                : 7
                : 6
                : 719-724
                [1 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Virology, , Erasmus Medical Center, ; Rotterdam, The Netherlands
                [2 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Pediatrics, , Erasmus Medical Center, ; Rotterdam, The Netherlands
                © Nature Publishing Group 2001

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                : 9 February 2001
                : 30 April 2001
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                © The Author(s), under exclusive licence to Springer Nature America, Inc. 2001



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