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J Virol, April 1998, p. 2871-2880, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Priming with Secreted Glycoprotein G of Respiratory Syncytial Virus (RSV) Augments Interleukin-5 Production and Tissue Eosinophilia after RSV Challenge

Teresa R. Johnson,1 Joyce E. Johnson,2 Sharon R. Roberts,3 Gail W. Wertz,4 Robert A. Parker,5 and Barney S. Graham1,6,*

Departments of Microbiology and Immunology,1 Pathology,2 and Medicine,6 Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Botany and Microbiology, Auburn University, Auburn,3 and Department of Microbiology, University of Alabama at Birmingham, Birmingham,4 Alabama; and Department of Medicine (Biostatistics), Harvard University School of Medicine, Boston, Massachusetts5

Received 12 September 1997/Accepted 22 December 1997

The respiratory syncytial virus (RSV) G glycoprotein promotes differentiation of type 2 CD4+ T lymphocytes and induces an eosinophilic response in lungs of RSV-infected mice. A unique feature of G is that a second initiation codon in the transmembrane region of the glycoprotein results in secretion of soluble protein from infected cells. Recombinant vaccinia viruses that express wild-type G (vvWT G), only secreted G (vvM48), or only membrane-anchored G (vvM48I) were used to define the influence of G priming on immunopathogenesis. Mice immunized with vvM48 had more severe illness following RSV challenge than did mice primed with vvWT G or vvM48I. Coadministration of purified G during priming with the construct expressing membrane-anchored G shifted immune responses following RSV challenge to a more Th2-like response. This was characterized by increased interleukin-5 in lung supernatants and an increase in G-specific immunoglobulin G1 antibodies. Eosinophils were present in the infiltrate of all mice primed with G-containing vectors but were greatest in mice primed with regimens including secreted G. These data suggest the form of G protein available for initial antigen processing and presentation is an important factor in promoting Th2-like immune responses, including the induction of lung eosinophilia. The ability of RSV to secrete G protein may therefore represent a viral strategy for immunomodulation and be a key determinant of disease pathogenesis.


* Corresponding author. Mailing address: A-4103 MCN, Vanderbilt University School of Medicine, 1161 21st Ave., Nashville, TN 37232-2582. Phone: (615) 343-3717. Fax: (615) 322-8222. E-mail: Barney.Graham{at}mcmail.vanderbilt.edu.




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