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Title: The role of the G protein in the pathogenesis of RSV
Author: Sadler, Ross
ISNI:       0000 0001 3544 6705
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2007
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The bovine and human respiratory syncytial viruses (RSV)s can cause severe lower respiratory tract infections. The surface glycoprotein, G protein, ofRSV is primarily thought to be an attachment protein and is an important protective antigen. Previous studies have shown the possibility ofthe G protein or regions within it playing a role in the pathogenesis ofRSV through modulation ofthe host immune system. In this report, the role ofthe G protein in the pathogenesis ofRSV in vivo was investigated. Infection of calves with recombinant (r) bovine (B) RSV expressing different forms of the G protein showed that the soluble form ofthe G protein (Gs) is essential for successful replication in the lungs. In addition, although rBRSV expressing only the membraneanchored G protein (Gm) was attenuated in the lungs and did not induce any pulmonary pathology, mucosal vaccination with this virus was able to protect calves against subsequent BRSV challenge. Studies using rBRSVs were also carried out in vitro by observing rBRSV infection of bovine airway epithelial cell cultures (BAEC). Previous work with recombinant vaccinia virus (rVV) has shown that the presence ofRSV G protein enhances replication ofrVV in the lungs of mice compared to control rVVs. To investigate which region(s) ofthe G protein may be responsible forJhis effect; mice were infected with rVV expressing the HRSV G protein containing deletions of specific regions. The replication ofrVV expressing the G protein lacking residues 193-205 (rVVG~193-105) was attenuated in the lungs of mice compared to rVVGwt. In addition rVVG~193-205 infection of mice induced lower amouptsofIFN-y in the broncho-alveolar lavage (BAL) compared to rVVGwt. The results described indicate that further investigation ofthe innate immune response induced following infection by different forms of RSV-G wiII contribute to a better understanding of how the adaptive immune response to RSV is influenced by the G protein.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available