Secreted respiratory syncytial virus G glycoprotein induces interleukin-5 (IL-5), IL-13, and eosinophilia by an IL-4-independent mechanism.

Abstract

The attachment glycoprotein G of respiratory syncytial virus (RSV) is produced as both membrane-anchored and secreted forms by infected cells. Immunization with secreted RSV G (Gs) or formalin-inactivated alumprecipitated RSV (FI-RSV) predisposes mice to immune responses involving a Th2 cell phenotype which results in more severe illness and pathology, decreased viral clearance, and increased pulmonary eosinophilia upon subsequent RSV challenge. These responses are associated with increased interleukin-4 (IL-4) production in FI-RSV-primed mice, and the responses are IL-4 dependent. RNase protection assays demonstrated that similar levels of IL-4 mRNA were induced after RSV challenge in mice primed with vaccinia virus expressing Gs (vvGs) or a construct expressing only membrane-anchored G (vvGr). However, upon RSV challenge, vvGs-primed mice produced significantly greater levels of IL-5 and IL-13 mRNA and protein than vvGr-primed mice. Administration of neutralizing anti-IL-4 antibody 11.B11 during vaccinia virus priming did not alter the levels of vvGs-induced IL-5, IL-13, pulmonary eosinophilia, illness, or RSV titers upon RSV challenge, although immunoglobulin G (IgG) isotype profiles revealed that more IgG2a was produced. vvGs-priming of IL-4-deficient mice demonstrated that G-induced airway eosinophilia was not dependent on IL-4. In contrast, airway eosinophilia induced by FI-RSV priming was significantly reduced in IL-4-deficient mice. Thus we conclude that, in contrast to FI-RSV, the secreted form of RSV G can directly induce IL-5 and IL-13, producing pulmonary eosinophilia and enhanced illness in RSV-challenged mice by an IL-4-independent mechanism.

• Authors: T R Johnson, B S Graham
• Journal: Journal of virology (J Virol) Vol. 73 Issue 10 Pg. 8485-95 (Oct 1999) ISSN: 0022-538X [Print] United States
• PMID: 10482601 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Viral
• HN Protein
• Interleukin-13
• Interleukin-5
• Viral Envelope Proteins
• Viral Proteins
• attachment protein G
• Interleukin-4

Topics

• Animals
• Antigens, Viral (immunology)
• Eosinophilia (immunology, virology)
• HN Protein
• Interleukin-13 (blood, immunology)
• Interleukin-4 (immunology)
• Interleukin-5 (blood, immunology)
• Mice
• Mice, Inbred BALB C
• Respiratory Syncytial Virus Infections (blood, immunology)
• Respiratory Syncytial Viruses
• Viral Envelope Proteins (immunology)
• Viral Proteins (immunology)