Suppression of human immunodeficiency virus type 1 replication by arginine deiminase of Mycoplasma arginini.
It was found previously that human immunodeficiency virus type 1 (HIV-1)-irrelevant CD8+ cytotoxic T lymphocytes (CTLs) from uninfected donors suppressed HIV-1 replication in a cell-contact-dependent manner. However, one of these CTL lines (CTL-3) also significantly suppressed HIV-1 replication through its supernatant. Here, the suppressive fraction from CTL-3 supernatant was purified and analysed by mass spectrometry. A protein band specific for the suppressive fraction was identified as arginine deiminase from Mycoplasma arginini, which catalyses the hydrolysis of arginine to citrulline. Addition of L-arginine or the use of antibiotics against mycoplasma restored supernatant-mediated but not cell-contact-dependent suppression of HIV-1 replication by CTL-3, clearly indicating that arginine deiminase of M. arginini in the supernatants suppressed HIV-1 replication, which is independent of CD8+ T-cell-mediated HIV-1 suppression via cell contact. Arginine deiminase is known to be a chemotherapeutic agent against arginine-requiring tumours and these results suggest that it also has potential application in antiviral therapy.
Kubo
Makoto
M
Japanese Foundation for AIDS Prevention, Tokyo 105-0001, Japan.|Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Nishitsuji
Hironori
H
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kurihara
Kiyoshi
K
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Hayashi
Takaya
T
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Masuda
Takao
T
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kannagi
Mari
M
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006867:Hydrolases / Q000378:metabolism / Q000494:pharmacology*; D013058:Mass Spectrometry; D009174:Mycoplasma / Q000201:enzymology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects*
D017077:Culture Media, Conditioned; D006867:Hydrolases; C019723:arginine deiminase