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Journal of Virology, June 2006, p. 5854-5861, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02671-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Cysteine-Rich Region and Secreted Form of the Attachment G Glycoprotein of Respiratory Syncytial Virus Enhance the Cytotoxic T-Lymphocyte Response despite Lacking Major Histocompatibility Complex Class I-Restricted Epitopes

Alexander Bukreyev,^1, Maria Elina Serra,^2, Federico R. Laham,^2,3 Guillermina A. Melendi,^2,3 Steven R. Kleeberger,⁴ Peter L. Collins,¹ and Fernando P. Polack^2,3*

National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland,¹ INFANT Fundacion, Buenos Aires, Argentina,² Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland,³ National Institute of Environmental Health Sciences, NIH, Research Triangle, North Carolina⁴

Received 20 December 2005/ Accepted 6 March 2006

The cytotoxic T-lymphocyte (CTL) response is important for the control of viral replication during respiratory syncytial virus (RSV) infection. The attachment glycoprotein (G) of RSV does not encode major histocompatibility complex class I-restricted epitopes in BALB/c mice (H-2^d). Furthermore, studies to date have described an absence of significant CTL activity directed against this protein in humans. Therefore, G previously was not considered necessary for the generation of RSV-specific CTL responses. In this study, we demonstrate that, despite lacking H-2^d-restricted epitopes, G enhances the generation of an effective CTL response against RSV. Furthermore, we show that this stimulatory effect is independent of virus titers and RSV-induced inflammation; that it is associated primarily with the secreted form of G; and that the effect depends on the cysteine-rich region of G (GCRR), a segment conserved in wild-type isolates worldwide. These findings reveal a novel function for the GCRR with potential implications for the generation of protective cellular responses and vaccine development.

A.B. and M.E.S. contributed equally to this study.

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