Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Negative-strand RNA viruses encode a single RNA-dependent RNA polymerase (RdRp) which transcribes and replicates the genome. The open reading frame encoding the RdRp from a virulent wild-type strain of rinderpest virus (RPV) was inserted into an expression plasmid. Sequences encoding enhanced green fluorescent protein (EGFP) were inserted into a variable hinge of the RdRp. The resulting polymerase was autofluorescent, and its activity in the replication/transcription of a synthetic minigenome was reduced. We investigated the potential of using this approach to rationally attenuate a virus by inserting the DNA sequences encoding the modified RdRp into a full-length anti-genome plasmid from which a virulent virus (rRPV(KO)) can be rescued. A recombinant virus, rRPV(KO)L-RRegfpR, which grew at an indistinguishable rate and to an identical titer as rRPV(KO) in vitro, was rescued. Fluorescently tagged polymerase was visible in large cytoplasmic inclusions and beneath the cell membrane. Subcutaneous injection of 10(4) TCID(50) of the rRPV(KO) parental recombinant virus into cattle leads to severe disease symptoms (leukopenia/diarrhea and pyrexia) and death by 9 days postinfection. Animals infected with rRPV(KO)L-RRegfpR exhibited transient leukopenia and mild pyrexia, and the only noticeable clinical signs were moderate reddening of one eye and a slight ocular-nasal discharge. Viruses that expressed the modified polymerase were isolated from peripheral blood lymphocytes and eye swabs. This demonstrates that a virulent morbillivirus can be attenuated in a single step solely by modulating RdRp activity and that there is not necessarily a correlation between virus growth in vitro and in vivo.
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PMID:Rational attenuation of a morbillivirus by modulating the activity of the RNA-dependent RNA polymerase. 1625 67

Since its first recognition, the 2009 pandemic influenza A (H1N1) virus rapidly spread worldwide. We observed the clinical characteristics of 167 hospitalized patients who were confirmed by testing pharyngeal or nasopharyngeal swabs with the use of a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay. The mean age of the 167 hospitalized patients was 4.1 years, and 58.7% were male. The most common symptoms and signs were fever (91.6%), cough (82.6%), pharyngeal congestion (95.2%), and swollen tonsils (34.1%). The major complications were bronchitis (19.2%), bronchial pneumonia (10.8%), neutropenia (49.7%), and leukopenia (38.9%). The duration of hospitalization, fever and the course of disease in the patients who were treated with oseltamivir were shorter than in those who were treated with ribavirin. All of the patients fully recuperated from the 2009 epidemic influenza A (H1N1) infection with one exception.
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PMID:Clinical features of 167 children with the novel influenza A (H1N1) virus infection in Xi'an, China. 2273 94