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

Microbes and Infection
Caroline F MaherPeter J M Openshaw

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 pro...Continue Reading

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Citations

Jul 16, 2005·Clinical Microbiology Reviews·Peter J M Openshaw, John S Tregoning
Sep 30, 2010·Immunotherapy·Lawrence M KauvarRalph A Tripp
Jul 16, 2005·Expert Opinion on Biological Therapy·Martin Cranage, Geraldine Taylor
Feb 1, 2008·Pharmacology & Therapeutics·Nicole G HansbroPhilip M Hansbro
Aug 28, 2007·Comparative Immunology, Microbiology and Infectious Diseases·Gilles MeyerFrançois Schelcher
Dec 18, 2015·Clinical and Vaccine Immunology : CVI·Patricio L AcostaFernando P Polack
Sep 28, 2006·Reviews in Medical Virology·S van Drunen Littel-van den HurkJ Kovacs-Nolan
Jan 30, 2007·Veterinary Research·Jean-Francois Valarcher, Geraldine Taylor
Aug 24, 2013·Expert Review of Respiratory Medicine·Patricia A JorqueraRalph A Tripp
Feb 15, 2008·The Journal of General Virology·Toby M WardWayne L Gray
Oct 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ellen J CollariniLawrence M Kauvar
Apr 5, 2020·Viruses·Megha Aggarwal, Richard K Plemper
Aug 11, 2021·Viruses·Larry J AndersonSuxiang Tong

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