Inhibitory effects of human interferons on the immortalization of human, but not rabbit, T lymphocytes by human T-lymphotropic virus type-I (HTLV-I).
The effects of human interferon (IFN)-alpha, -beta, and -gamma on the immortalization of human and rabbit lymphocytes by human T-lymphotropic virus type-I (HTLV-I) have been investigated. The immortalization of human peripheral-blood lymphocytes co-cultured with lethally X-ray-irradiated HTLV-I-producer cells, MT-2, was blocked in the presence of more than 40 u/ml human recombinant IFN-alpha or more than 200 u/ml human natural type IFN-beta. However, rhIFN-gamma did not block immortalization by HTLV-I even at higher doses. On the other hand, the presence of high doses of hIFN-alpha, -beta, or -gamma did not exhibit any biological effect on the immortalization of rabbit peripheral-blood lymphocytes co-cultured with lethally X-ray-irradiated MT-2 cells. Integration of the full length of HTLV-I genome was detected in every transformant by Southern blot analysis. All cell lines established were CD4+/CD8 divided by T-lymphocytes, except for one cell line of CD4+/CD8+. Morphologically intact HTLV-I production was observed by electron microscopy in these cells. Our results indicate that HTLV-I released under the strongly suppressed condition in the presence of IFNs remains active and able to immortalize T lymphocytes. It is also suggested that immortalization of human T lymphocytes by HTLV-I can be inhibited by the antiviral state induced by the treatment with low doses of hIFN-alpha and -beta, whereas immortalization of rabbit T lymphocytes is not inhibited because of the species specificity of hIFNs.
Oka
T
T
Department of Pathology, Kochi Medical School, Japan.
Iwata
J
J
Furihata
M
M
Sonobe
H
H
Miyoshi
I
I
Ohtsuki
Y
Y
D000818:Animals; D015139:Blotting, Southern; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits; D011994:Recombinant Proteins; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D016662:Virus Integration
D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma