Recombinant respiratory syncytial virus lacking secreted glycoprotein G is attenuated, non-pathogenic but induces protective immunity

Caroline F. Maher, Tracy Hussell, Edward Blair, Christopher J A Ring, Peter J M Openshaw

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Respiratory syncytial virus (RSV) causes intense pulmonary inflammatory responses in some infected infants. The surface attachment protein 'G' of RSV has membrane-bound and secreted forms and shows homology to the CX3C chemokine fractalkine. Using recombinant techniques, we generated replication-competent recombinant clonal RSV expressing normal G proteins ('rRSV') or only the membrane-bound form of G ('Gmem rRSV'). Both recombinants grew well in HEp-2 cells, but after primary intranasal infection in mice, pulmonary Gmem rRSV replication was reduced tenfold compared to parental or rRSV; moreover, CCL2 and CCL5 production was greatly reduced and no apparent disease or pulmonary cellular infiltration was observed. However, Gmem rRSV-infected mice developed good antibody responses and were fully protected against subsequent intranasal challenge with parental virus. Even in mice sensitized to G by cutaneous infection with recombinant vaccinia expressing G, intranasal challenge with Gmem rRSV caused insignificant disease. We conclude that secreted G is a key viral product assisting virus replication in vivo, enhancing CCL2 and CCL5 production and promoting illness. Engineered RSV mutants lacking the ability to secrete G are thus promising vaccine candidates. © 2004 Elsevier SAS. All rights reserved.
    Original languageEnglish
    Pages (from-to)1049-1055
    Number of pages6
    JournalMicrobes and Infection
    Volume6
    Issue number12
    DOIs
    Publication statusPublished - Oct 2004

    Keywords

    • Asthma
    • Bronchiolitis, viral
    • Common cold
    • Immunity, mucosal
    • Pneumovirinae

    Fingerprint

    Dive into the research topics of 'Recombinant respiratory syncytial virus lacking secreted glycoprotein G is attenuated, non-pathogenic but induces protective immunity'. Together they form a unique fingerprint.

    Cite this