Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells.
To examine the effects of macrolide antibiotics on RS virus infection in airways, human tracheal epithelial cells were pre-treated with bafilomycin A(1) and clarithromycin, and infected with RS virus. Viral titers in supernatant fluids and RNA of RS virus, and concentrations of cytokines in supernatant fluids, including interleukin-6 increased with time after infection. Bafilomycin A(1) and clarithromycin reduced viral titers in supernatant fluids of RS virus, RNA of RS virus, the susceptibility to RS virus infection, and concentrations of cytokines induced by virus infection. N-acetyl-S-geranylgeranyl-L-cysteine, an inhibitor for a small GTP binding protein of RhoA, isoform A of the Ras-homologus (Rho) family, an active form of which is associated with RS virus infection via binding to its fusion protein (F protein), reduced viral titers in supernatant fluids and RNA of RS virus. Bafilomycin A(1) and clarithromycin inhibited RhoA activation induced by lysophosphatidic acid in the cells. Fasudil, an inhibitor of Rho kinase, also reduced viral titers in supernatant fluids and RNA of RS virus. These findings suggest that macrolide antibiotics may inhibit RS virus infection, partly through the reduced expression of F protein receptor, activated RhoA, and the inhibition of subsequent Rho kinase activation in human airway epithelial cells.
Asada
Masanori
M
Department of Geriatrics and Gerontology, Tohoku University School of Medicine, Sendai, Japan.
Yoshida
Motoki
M
Suzuki
Tomoko
T
Hatachi
Yukimasa
Y
Sasaki
Takahiko
T
Yasuda
Hiroyasu
H
Nakayama
Katsutoshi
K
Nishimura
Hidekazu
H
Nagatomi
Ryoichi
R
Kubo
Hiroshi
H
Yamaya
Mutsuo
M
D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000166:cytology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D017291:Clarithromycin