Human T-cell leukemia virus type I infects human lung epithelial cells and induces gene expression of cytokines, chemokines and cell adhesion molecules.
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-kappaB 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.


CONCLUSIONS
Our results suggest that HTLV-I infects lung epithelial cells, with subsequent production of cytokines, chemokines and cell adhesion molecules through induction of NF-kappaB and AP-1. These changes can contribute to the clinical features of HTLV-I-related pulmonary diseases.
Teruya
Hiromitsu
H
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan. hiromitsu20@hotmail.com
Tomita
Mariko
M
Senba
Masachika
M
Ishikawa
Chie
C
Tamayose
Maki
M
Miyazato
Akiko
A
Yara
Satomi
S
Tanaka
Yuetsu
Y
Iwakura
Yoichiro
Y
Fujita
Jiro
J
Mori
Naoki
N
D033961:Adaptor Protein Complex 1 / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D004279:DNA, Viral / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016356:Gene Products, tax / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D011533:Proviruses / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000821:virology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis
D033961:Adaptor Protein Complex 1; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004279:DNA, Viral; D016356:Gene Products, tax; D016328:NF-kappa B; D054301:gag Gene Products, Human Immunodeficiency Virus; C060955:p19 protein, Human T-lymphotropic virus 1; C514970:tax protein, Human T-lymphotrophic virus 1