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.
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.
Bukreyev
Alexander
A
National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Serra
Maria Elina
ME
Laham
Federico R
FR
Melendi
Guillermina A
GA
Kleeberger
Steven R
SR
Collins
Peter L
PL
Polack
Fernando P
FP
D000818:Animals; D003545:Cysteine; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; C502275:G glycoprotein, Respiratory syncytial virus; D015395:Histocompatibility Antigens Class I; D014760:Viral Fusion Proteins; D003545:Cysteine