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Journal of Virology, December 2008, p. 12191-12204, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01604-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Secreted Form of Respiratory Syncytial Virus G Glycoprotein Helps the Virus Evade Antibody-Mediated Restriction of Replication by Acting as an Antigen Decoy and through Effects on Fc Receptor-Bearing Leukocytes{triangledown}

Alexander Bukreyev,1* Lijuan Yang,1 Jens Fricke,1 Lily Cheng,2 Jerrold M. Ward,2 Brian R. Murphy,1 and Peter L. Collins1

Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Dr., Bethesda, Maryland 20892,1 Infectious Diseases Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 208922

Received 28 July 2008/ Accepted 2 October 2008

Respiratory syncytial virus (RSV) readily infects and reinfects during infancy and throughout life, despite maternal antibodies and immunity from prior infection and without the need for significant antigenic change. RSV has two neutralization antigens, the F and G virion glycoproteins. G is expressed in both membrane-bound (mG) and secreted (sG) forms. We investigated whether sG might act as a decoy for neutralizing antibodies by comparing the in vitro neutralization of wild-type (wt) RSV versus recombinant mG RSV expressing only mG. wt RSV indeed was less susceptible than mG RSV to monovalent G-specific and polyvalent RSV-specific antibodies, whereas susceptibility to F-specific antibodies was equivalent. This difference disappeared when the virus preparations were purified to remove sG. Thus, sG appears to function as a neutralization decoy. We evaluated this effect in vivo in mice by comparing the effects of passively transferred antibodies on the pulmonary replication of wt RSV versus mG RSV. Again, wt RSV was less sensitive than mG RSV to G-specific and RSV-specific antibodies; however, a similar difference was also observed with F-specific antibodies. This confirmed that sG helps wt RSV evade the antibody-dependent restriction of replication but indicated that in mice, it is not acting primarily as a decoy for G-specific antibodies, perhaps because sG is produced in insufficient quantities in this poorly permissive animal. Rather, we found that the greater sensitivity of mG versus wt RSV to the antiviral effect of passively transferred RSV antibodies required the presence of inflammatory cells in the lung and was Fc{gamma} receptor dependent. Thus, sG helps RSV escape the antibody-dependent restriction of replication via effects as an antigen decoy and as a modulator of leukocytes bearing Fc{gamma} receptors.

* Corresponding author. Mailing address: LID, NIAID, NIH, 50 South Drive, Room 6505, Bethesda, MD 20892-8007. Phone: (301) 594-1854. Fax: (301) 496-8312. E-mail: abukreyev{at}nih.gov

{triangledown} Published ahead of print on 8 October 2008.

Journal of Virology, December 2008, p. 12191-12204, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01604-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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