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 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.
Johnson
T R
TR
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2582, USA.
Johnson
J E
JE
Roberts
S R
SR
Wertz
G W
GW
Parker
R A
RA
Graham
B S
BS
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018893:Bronchoalveolar Lavage; D002460:Cell Line; D004802:Eosinophilia / Q000276:immunology*; D015707:HN Protein; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000096:biosynthesis / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication; D015431:Weight Loss
D000914:Antibodies, Viral; D015707:HN Protein; D007074:Immunoglobulin G; D015848:Interleukin-5; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G; D007371:Interferon-gamma