PRIMING WITH SECRETED GLYCOPROTEIN-G OF RESPIRATORY SYNCYTIAL VIRUS (RSV) AUGMENTS INTERLEUKIN-5 PRODUCTION AND TISSUE EOSINOPHILIA AFTER RSV CHALLENGE

The respiratory syncytial virus (RSV) G glycoprotein promotes differen tiation of type 2 CD4(+) T lymphocytes and induces an eosinophilic res ponse in lungs of RSV-infected mice. A unique feature of G is that a s econd initiation codon in the transmembrane region of the glycoprotein results in secretion of soluble protein from infected cells. Recombin ant vaccinia viruses that express wild-type G (vvWT G), only secreted G (vvM48), or only membrane-anchored G (vvM48I) were used to define th e influence of G priming on immunopathogenesis. Mice immunized with vv M48 had more severe illness following RSV challenge than did mice prim ed with vvWT G or vvM48I. Coadministration of purified G during primin g with the construct expressing membrane-anchored G shifted immune res ponses following RSV challenge to a more Th2-like response. This was c haracterized by increased interleukin-5 in lung supernatants and an in crease in G-specific immunoglobulin G1 antibodies. Eosinophils were pr esent in the infiltrate of all mice primed with G-containing vectors b ut were greatest in mice primed with regimens including secreted G. Th ese data suggest the form of G protein available for initial antigen p rocessing and presentation is an important factor in promoting Th2-lik e immune responses, including the induction of lung eosinophilia. The ability of RSV to secrete G protein may therefore represent a viral st rategy for immunomodulation and be a key determinant of disease pathog enesis.