Research
Human T-cell leukemia virus type I infects human lung epithelial cells and induces gene expression of cytokines, chemokines and cell adhesion molecules
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* Corresponding author: Naoki Mori n-mori@med.u-ryukyu.ac.jp
1 Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan
2 Division of Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan
3 Department of Pathology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Japan
4 Division of Child Health and Welfare, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan
5 The Japanese Society for the Promotion of Science (JSPS), Japan
6 Department of Infectious Diseases and Infection Control, International Medical Center, Saitama Medical School, 1397-1 Yamane Hidaka, Saitama, Japan
7 Division of Immunology, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan
8 Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan
Retrovirology 2008, 5:86 doi:10.1186/1742-4690-5-86
Published: 22 September 2008Abstract
Background
Human T-cell leukemia virus type I (HTLV-I) is associated with pulmonary diseases, characterized by bronchoalveolar lymphocytosis, which correlates with HTLV-I proviral DNA in carriers. HTLV-I Tax seems to be involved in the development of such pulmonary diseases through the local production of inflammatory cytokines and chemokines in T cells. However, little is known about induction of these genes by HTLV-I infection in lung epithelial cells.
Results
We tested infection of lung epithelial cells by HTLV-I by coculture studies in which A549 alveolar and NCI-H292 tracheal epithelial cell lines were cocultured with MT-2, an HTLV-I-infected T-cell line. Changes in the expression of several cellular genes were assessed by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. Coculture with MT-2 cells resulted in infection of lung epithelial cells as confirmed by detection of proviral DNA, HTLV-I Tax expression and HTLV-I p19 in the latter cells. Infection was associated with induction of mRNA expression of various cytokines, chemokines and cell adhesion molecule. NF-κB and AP-1 were also activated in HTLV-I-infected lung epithelial cells. In vivo studies showed Tax protein in lung epithelial cells of mice bearing Tax and patients with HTLV-I-related pulmonary diseases.
Conclusion
Our results suggest that HTLV-I infects lung epithelial cells, with subsequent production of cytokines, chemokines and cell adhesion molecules through induction of NF-κB and AP-1. These changes can contribute to the clinical features of HTLV-I-related pulmonary diseases.