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NITROTYROSINE INHIBITS RESPIRATORY SYNCTIAL VIRUS-INDUCED RANTES PRODUCTION IN HUMAN BRONCHIAL EPITHELIAL CELLS
Citation:
Huang, YuhChin T, S E. Becker, J M. Soukup, Z. Li, J. CARSON, AND L. ZHHOUWEI. NITROTYROSINE INHIBITS RESPIRATORY SYNCTIAL VIRUS-INDUCED RANTES PRODUCTION IN HUMAN BRONCHIAL EPITHELIAL CELLS. American Journal of Physiology - Lung Cellular and Molecular Physiology. American Physiological Society, Bethesda, MD, 288(4):L988-996, (2005).
Impact/Purpose:
We tested the hypothesis that 3-Nitrotyrosine would inhibit respiratory syncytial virus (RSV) infection and investigated the mechanisms
Description:
3-Nitrotyrosine (NO2Tyr) produced during inflammation can substitute the C-terminus tyrosine of a-tubulin post-translationally altering microtubular functions. Since propagation of respiratory syncytial virus (RSV) infection may require an intact microtubular activity, we tested the hypothesis that NO2Tyr would inhibit RSV-induced RANTES production and investigated the mechanisms. RSV-infected human bronchial epithelial cells (BEAS-2B) released viral particles and RANTES in a time- and dose-dependent manner, and intracellular RSV proteins co-precipitated and co-localized with a-tubulin. NO2Tyr attenuated the release of RANTES and viral particles, decreased a-tubulin-associated RSV proteins and co-localized with RSV. NO2Tyr increased nitrotyrosinated a-tubulin and co-localized with a-tubulin but did not affect microtubule stabilization by acetylation. 3-Chlorotyrosine, another L-tyrosine derivative, reversed the NO2Tyr-induced inhibition competitively. NO2Tyr inhibited serine phosphorylation of RSV P protein, a casein kinase II (CKII)-dependent process, and the RSV-induced shift of the unphosphorylated form I of interferon regulatory factor 3 (IRF-3) to the phosphorylated form II. Two CKII inhibitors, apigenin and heparin, also inhibited serine phosphorylation of RSV P protein, the RSV-induced accumulation of IRF-3(II) and RANTES production. These results indicated that NO2Tyr, by nitrotyrosinating a-tubulin, may modulate microtubular surface properties and interfere with signaling of RANTES production via inhibition of CKII and IRF-3 activation during RSV infection.
Keywords: RANTES, microtubules, tubulin, IRF-3, casein kinase