Abstract
The present study shows the effect of human interferon β (IFNβ) on the susceptibility of highly purified cord blood CD4+ T cells to infection with the human T cell leukaemia virus type I (HTLV-I). Unfractionated cord blood mononuclear cells (CBMC), or a separated CD4+ T cell subpopulation (CBCD4) were exposed to HTLV-I by cocultivation with a chronically infected virus-donor cell line. The results show that presence of proviral DNA as well as virus transcription was markedly reduced by IFNβ in both populations, indicating that this cytokine protects not only unfractionated CBMC but also purified CBCD4 cells from virus infection. Moreover IFNβ treatment caused 60%–80% inhibition of virus expression in CBCD4, assayed as the presence of virus core protein p19. This study demonstrates that IFNβ is able to inhibit HTLV-I infection of CBMC through a mechanism that does not necessarily involve cell-mediated natural or antigen-dependent immunity afforded by CBMC subpopulations distinct from targets of HTLV-I infection. Therefore it is reasonable to conclude that IFNβ has a direct protective effect on CBCD4, through induction of antiviral resistance/activity in target cells.
Key words: HTLV-I; Interferon; Cord blood; 2′,5′-oligo(A) synthetase
References
- 1.Akagi T, Ohtsuki Y, Shirasaishi Y, Miyoshi I. Transformation of human fetal thymus and spleen lymphocytes by human T-cell leukemia virus type I. Acta Med Okayama. 1985;39:155. doi: 10.18926/AMO/31513. [DOI] [PubMed] [Google Scholar]
- 2.Avery RJ, Norton JD, Jones JS, Burke DC, Morris AG. Interferon inhibits transformation by murine sarcoma viruses before integration of provirus. Nature. 1980;288:93. doi: 10.1038/288093a0. [DOI] [PubMed] [Google Scholar]
- 3.Clapham P, Nagy K, Cheingson-Popov R, Exley M, Weiss RA. Productive infection and cell free transmission of human T-Cell leukaemia virus in nonlymphoid cell line. Science. 1983;222:1125. doi: 10.1126/science.6316502. [DOI] [PubMed] [Google Scholar]
- 4.D'Onofrio C, Perno CF, Mazzetti P, Graziani G, Caliò R, Bonmassar E. Depression of early phase of HTLV-I infection in vitro mediated by human interferon beta. Br J Cancer. 1988;57:481. doi: 10.1038/bjc.1988.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.D'Onofrio C, Pesce CD, Fontana T, Ciprani F, Bonmassar E, Caliò R. Modulation of the cell mediated immune function by interferon alpha, beta, or gamma can partially reverse the immune suppression induced by HTLV-I in human cord blood cultures. Cancer Immunol Immunother. 1990;31:213. doi: 10.1007/BF01789171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.D'Onofrio C, Alvino E, Garaci E, Bonmassar E, Santoro MG. Selection of HTLV-I positive clones is prevented by prostaglandin A in infected cord blood cultures. Br J Cancer. 1990;61:207. doi: 10.1038/bjc.1990.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.D'Onofrio C, Peci E, Alvino E, Caliò R, Bonmassar E. Differential interference of alpha, beta, or gamma interferons with HTLV-I integration and expression in vitro. Ann Ist Sup Sanità. 1991;27:127. [PubMed] [Google Scholar]
- 8.D'Onofrio C, Franzese O, Puglianiello A, Peci E, Lanzilli G, Bonmassar E. Antiviral activity of individual versus combined treatments with interferon alpha, beta and gamma on early infection with HTLV-I in vitro. Int J Immunopharmacol. 1992;14:1069. doi: 10.1016/0192-0561(92)90152-b. [DOI] [PubMed] [Google Scholar]
- 9.Gallo RC. The human T-cell leukemia/lymphotropic retrovirus (HTLV-I) family: past present and future. Cancer Res. 1985;45:4524. [PubMed] [Google Scholar]
- 10.Gaudernack G, Leivestad T, Ugelstad J, Thorsby E. Isolation of pure functionally active CD8+ T cells. Positive selection with monoclonal antibodies directly conjugated to monosized magnetic microspheres. J Immunol Methods. 1986;90:179. doi: 10.1016/0022-1759(86)90074-8. [DOI] [PubMed] [Google Scholar]
- 11.Gazzolo L, Duc Dodon M. Direct activation of resting T lymphocytes by human T-lymphotropic virus type I. Nature. 1988;326:714. doi: 10.1038/326714a0. [DOI] [PubMed] [Google Scholar]
- 12.Hattori T, Uchiyama T, Toibana T, Takatsuki K, Uchino H. Surface phenotype of Japanese adult T cell leukemia cells characterized by monoclonal antibodies. Blood. 1981;58:645. [PubMed] [Google Scholar]
- 13.Hoxie JA, Matthews DM, Cines DB. Infection of human endhotelial cells by human T-cell leukemia virus type I. Proc Natl Acad Sci USA. 1984;81:7591. doi: 10.1073/pnas.81.23.7591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kimata JT, Ratner L. Temporal regulation of viral and cellular gene expression during Human T-lymphotropic virus type I mediated lymphocyte immortalization. J Virol. 1991;65:4398. doi: 10.1128/jvi.65.8.4398-4407.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Lavi S, Etkin S. Carcinogen-mediated induction of SV40 DNA syntesis in SV40 transformed Chinese hamster embryo cells. Carcinogenesis. 1981;2:417. doi: 10.1093/carcin/2.5.417. [DOI] [PubMed] [Google Scholar]
- 16.Macchi B, Allavena P, Ortaldo J, Rossi P, Gallo RC, Bonmassar E. In vitro susceptibility of different human T subpopulations and resistance of large granular lymphocytes to HTLV-I infection. Int J Cancer. 1987;40:1. doi: 10.1002/ijc.2910400102. [DOI] [PubMed] [Google Scholar]
- 17.Macchi B, D'Onofrio C, Labianca RA, Bonmassar E. Mononuclear cells from peripheral blood of adult donors and from neonatal cord blood are equally protected by alfa and beta interferons against infection with HTLV-I. Pharmacol Res. 1990;22:503. doi: 10.1016/1043-6618(90)90756-4. [DOI] [PubMed] [Google Scholar]
- 18.Macchi B, Caronti B, Pezzella F, Bonmassar E, Lauro G.M. Effect of HTLV-I exposure on cells of neuroectodermic origin. Acta Neuropathol. 1990;81:670. doi: 10.1007/BF00296378. [DOI] [PubMed] [Google Scholar]
- 19.Markhman PD, Salahuddin Z, Macchi B, Robert Guroff M, Gallo RC. Transformation of different phenotypic types of human bone marrow T-lymphocytes by HTLV-I. Int J Cancer. 1986;33:13. doi: 10.1002/ijc.2910330104. [DOI] [PubMed] [Google Scholar]
- 20.McFarlin DE, Koprowski H. Neurological disorders associated with HTLV-I. Curr Top Microbiol Immunol. 1990;160:99. [PubMed] [Google Scholar]
- 21.Minks MA, Bevin S, Maroney PA, Baglioni C. Synthesis of 2′–5′oligo(A) in extract of interferon-treated HeLa cells. J Biol Chem. 1979;254:5058. [PubMed] [Google Scholar]
- 22.Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Outsuki Y, Shirashy Y, Nagata K, Hinuma Y. Detection of type C retrovirus particles on a cord blood T-cell line derived by cocultivation of normal human lymphocytes and human leukemic T-cells. Nature. 1981;296:770. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
- 23.Oka T, Ohtsuki Y, Sonobe H, Furihata M, Miyoshy I. Suppressive effects of interferons on the production and release of human T-lymphotropic virus type I (HTLV-I) Arch Virol. 1990;115:63. doi: 10.1007/BF01310623. [DOI] [PubMed] [Google Scholar]
- 24.Oka T, Iwata J, Furihata M, Sonobe H, Miyoshi I, Ohtsuki Y. Inhibitory effects of human interferons on the immortalization of human, but not rabbit, T lymphocytes by human T-lymphotropic virus type I (HTLV-I) Int J Cancer. 1992;51:915. doi: 10.1002/ijc.2910510614. [DOI] [PubMed] [Google Scholar]
- 25.Paeratakul P, De Stasio PR, Taylor MW. A fast sensitive method for detecting viral RNA in mammalian cells. J Virol. 1988;62:1132. doi: 10.1128/jvi.62.4.1132-1135.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Poiesez BJ, Ruscetti FW, Gadzar FA, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retroviral particles from fresh and cultured lymphocytes of a patient with cutaneous T cell lymphoma. Proc Natl Acad Sci USA. 1980;77:7415. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Richardson JH, Edwards AJ, Cruickshank JK, Rudge P, Dalgleish AG. In vivo cellular tropism of Human T-cell leukemia virus type I. J Virol. 1990;64:5682. doi: 10.1128/jvi.64.11.5682-5687.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Robert-Guroff M, Ruscetti FW, Posner BJ, Gallo RC. Detection of the human T-cell lymphoma virus p19 in cells of some patients with cutaneous T-cell lymphoma and leukemia using a monoclonal antibody. J Exp Med. 1981;154:1957. doi: 10.1084/jem.154.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Schüpbach J. Human retrovirology: facts and concepts. Berlin Heidelberg New York: Springer; 1989. p. 1. [PubMed] [Google Scholar]
- 30.Shirazi Y, Pitha PM. Alpha interferon inhibits early stages of the human deficiency virus type I replication cycle. J Virol. 1992;66:1321. doi: 10.1128/jvi.66.3.1321-1328.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Taylor JL, Grossberg SE. Recent progress in interferon research: molecular mechanism of regulation, action and virus circumvention. Virus Res. 1990;15:1. doi: 10.1016/0168-1702(90)90010-9. [DOI] [PubMed] [Google Scholar]
- 32.Yoshida M, Seiki M, Yamaguchi Y, Tokatsuki K. Monoclonal integration of human T cell leukemia provirus in all primary tumours of adult T cell leukemia suggests causative role of human T cell leukemia virus in disease. Proc. Natl Acad Sci USA. 1984;81:2534. doi: 10.1073/pnas.81.8.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]