The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P

Abstract

Respiratory syncytial virus (RSV) infection in the neonate can alter respiratory rates, i.e., lead to episodes of apnea. We show that RSV G glycoprotein reduces respiratory rates associated with the induction of substance P (SP) and G glycoprotein-CX3CR1 interaction, an effect that is inhibited by treatment with anti-G glycoprotein, anti-SP, or anti-CX3CR1 monoclonal antibodies. These data suggest new approaches for treating some aspects of RSV disease.

FIG. 1.

Respiratory rates associated with G and F glycoproteins. (A) G glycoprotein. BALB/c mice were i.v. treated with purified RSV G glycoprotein isolated from RSV-infected Vero cells (G10, G100, and G1000, respectively) or PBS. ⋆, significant differences (P < 0.05) compared with PBS-treated group. (B) Comparison of F and G glycoproteins. BALB/c mice were i.v. treated with purified RSV F (F100) or G (G100) glycoprotein or uninfected VCL control. ⋆, significant differences (P < 0.05) compared with VCL-treated group. The mean respiratory rates ± standard errors from eight individual BALB/c mice were determined at time points between 0.25 and 4 h posttreatment.

FIG. 2.

Antibody treatment and respiratory rates. (A) BALB/c mice were i.v. treated with purified RSV G glycoprotein (G100) following i.p. administration of either PBS (G100/PBS) or anti-G glycoprotein (G100/anti-G) or anti-F glycoprotein monoclonal antibody (G100/anti-F). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. (B) BALB/c mice were i.v. treated with purified RSV G glycoprotein (G100) following i.p. administration of either PBS (G100/PBS) or anti-SP monoclonal antibody (G100/anti-SP). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. (C) BALB/c mice were i.v. treated with purified RSV G glycoprotein (G100) following i.p. administration of either PBS (G100/PBS) or anti-CX3CR1 monoclonal antibody (G100/anti-CX3CR1). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. The mean respiratory rates ± standard errors from eight individual BALB/c mice were determined at time points between 0.25 and 4 h posttreatment.

FIG. 2.

Antibody treatment and respiratory rates. (A) BALB/c mice were i.v. treated with purified RSV G glycoprotein (G100) following i.p. administration of either PBS (G100/PBS) or anti-G glycoprotein (G100/anti-G) or anti-F glycoprotein monoclonal antibody (G100/anti-F). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. (B) BALB/c mice were i.v. treated with purified RSV G glycoprotein (G100) following i.p. administration of either PBS (G100/PBS) or anti-SP monoclonal antibody (G100/anti-SP). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. (C) BALB/c mice were i.v. treated with purified RSV G glycoprotein (G100) following i.p. administration of either PBS (G100/PBS) or anti-CX3CR1 monoclonal antibody (G100/anti-CX3CR1). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. The mean respiratory rates ± standard errors from eight individual BALB/c mice were determined at time points between 0.25 and 4 h posttreatment.

FIG. 3.

G glycoprotein with an altered CX3C site does not reduce respiratory rates. BALB/c mice were i.v. treated with FKN, G glycoprotein with a deletion in the CX3C motif (GDCYS), or G glycoprotein with an Ala insertion in the CX3C motif (G-CX4C). ⋆, significant differences (P < 0.05) compared with G100/PBS-treated group. #, significant differences (P < 0.05) compared with PBS-treated group. The mean respiratory rates ± standard errors from eight individual BALB/c mice were determined at time points between 0.25 and 4 h posttreatment.