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Journal of Virology, February 2000, p. 1614-1622, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

Ralph A. Tripp,* Deborah Moore, Jorn Winter, and Larry J. Anderson

Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333

Received 7 September 1999/Accepted 1 November 1999

A distinct clinical presentation of respiratory syncytial virus (RSV) infection of humans is bronchiolitis, which has clinical features similar to those of asthma. Substance P (SP), a tachykinin neuropeptide, has been associated with neurogenic inflammation and asthma; therefore, we chose to examine SP-induced inflammation with RSV infection. In this study, we examined the production of pulmonary SP associated with RSV infection of BALB/c mice and the effect of anti-SP F(ab)2 antibodies on the pulmonary inflammatory response. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatment of RSV-infected mice with anti-SP F(ab)2 antibodies suggested that SP may alter the natural killer cell response to primary and secondary infection. In mice challenged after formalin-inactivated RSV vaccination, SP appears to markedly enhance pulmonary eosinophilia as well as increase polymorphonuclear cell trafficking to the lung. Based on studies with a strain of RSV that lacks the G and SH genes, the SP response to RSV infection appears to be associated with G and/or SH protein expression. These data suggest that SP may be an important contributor to the inflammatory response to RSV infection and that anti-SP F(ab)2 antibodies might be used to ameliorate RSV-associated disease.

* Corresponding author. Mailing address: Centers for Disease Control and Prevention, 1600 Clifton Rd., MS G-09, Atlanta, GA 30333. Phone: (404) 639-3427. Fax: (404) 639-1307. E-mail: rgt3{at}cdc.gov.

Journal of Virology, February 2000, p. 1614-1622, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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