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Title: Delayed effects of respiratory syncytial virus infection
Author: O'Donnell, Diarmuid Rodney
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1997
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Respiratory Syncytial (RS) virus is the most important respiratory pathogen of infants. The role of RS virus, in the pathogenesis of wheezing and asthma has been a topic of medical interest for many years. Many questions about the pathogenesis of RS virus disease remain unanswered. With new techniques, answers to some of these questions can be attempted. In this thesis, novel techniques were used in studies of RS virus infected infants, children and adults, and mice. Using a nested reverse transcriptase polymerase chain reaction (RT-PCR), it was shown that cell associated viraemia occurs in some infants hospitalised with bronchiolitis but that RS virus cannot be detected in serum or cerebrospinal fluid. RT-PCR was also used to determine, first, the frequency of RS virus in nasopharyngeal aspirates from children admitted with respiratory illnesses, and, in bronchoalveolar lavage fluid from adults infected with human immunodeficiency virus being investigated for unexplained respiratory symptoms. In mice, RT-PCR showed that RS virus persists for at least 100 days after acute infection. Almost all the isolates sequenced from these mice contained an unchanged dominant epitope for cytotoxic lymphocyte (CTL) recognition and all the mice tested had vigorous CTL recognising this epitope. A mutant epitope was also detected, but extensive studies using synthetic peptides did not show interference or inhibition of CTL responses by this mutant. The effect of RS and influenza A virus infections on the immune response to an inhaled protein antigen (ovalbumin) was studied. In the presence of viral infection, acute anaphylaxis and exaggerated TH2 responses to ovalbumin were shown, without the use of adjuvant. This comprises a novel finding of possible clinical significance. By showing viral persistence and altered responses to other antigens, these studies may in part explain the delayed effects of RS virus infection in man.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available