INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS AND GROWTH OF INFECTED T-CELLS BY THE IMMUNOSUPPRESSIVE DRUGS CYCLOSPORINE-A AND FK-506

被引:121
作者
KARPAS, A
LOWDELL, M
JACOBSON, SK
HILL, F
机构
[1] ROYAL LONDON HOSP,DEPT IMMUNOL,LONDON E1 1BB,ENGLAND
[2] ADDENBROOKES HOSP,CLIN MICROBIOL PUBL HLTH LAB,CAMBRIDGE CB2 2QQ,ENGLAND
关键词
ANTIVIRAL AGENTS; AIDS;
D O I
10.1073/pnas.89.17.8351
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The effects of the immunosuppressive drugs cyclosporin A and FK 506 were studied on cells chronically infected with human immunodeficiency virus type 1 (HIV-1) as well as on uninfected and newly infected cells. When cells chronically infected with HIV-1 or with HIV-2 were cocultivated with uninfected cells in the presence of cyclosporin A or FK 506 there was a delay in the formation of syncytia and of cytopathic effects. This inhibitory effect was not due to decreased membrane expression of CD4. In addition, there was an almost-equal-to 100-fold reduction in the yield of infectious HIV-1 when the infected cells were grown in the presence of these drugs, a finding consistent with other evidence of decreased HIV expression. Both drugs were found to inhibit the growth of chronically infected cells at concentrations that did not inhibit the growth of the uninfected cells. These results, demonstrating that cyclosporin A and FK 506 interfere with HIV production and selectively inhibit the growth of infected cells, suggest that they may be useful in the treatment of this infection and indicate further cellular targets for antiviral agents.
引用
收藏
页码:8351 / 8355
页数:5
相关论文
共 27 条
  • [1] EFFECTS OF CYCLOSPORIN ON T-CELL SUBSETS IN HUMAN IMMUNODEFICIENCY VIRUS-DISEASE
    ANDRIEU, JM
    EVEN, P
    VENET, A
    TOURANI, JM
    STERN, M
    LOWENSTEIN, W
    AUDROIN, C
    EME, D
    MASSON, D
    SORS, H
    ISRAELBIET, D
    BELDJORD, K
    [J]. CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1988, 47 (02): : 181 - 198
  • [2] HIV-INFECTION AND BONE-MARROW TRANSPLANTATION
    BANDINI, G
    RE, MC
    ROSTI, G
    BELARDINELLI, AR
    [J]. LANCET, 1991, 337 (8750) : 1163 - 1164
  • [3] ISOLATION OF A T-LYMPHOTROPIC RETROVIRUS FROM A PATIENT AT RISK FOR ACQUIRED IMMUNE-DEFICIENCY SYNDROME (AIDS)
    BARRESINOUSSI, F
    CHERMANN, JC
    REY, F
    NUGEYRE, MT
    CHAMARET, S
    GRUEST, J
    DAUGUET, C
    AXLERBLIN, C
    VEZINETBRUN, F
    ROUZIOUX, C
    ROZENBAUM, W
    MONTAGNIER, L
    [J]. SCIENCE, 1983, 220 (4599) : 868 - 871
  • [4] ISOLATION OF A NEW HUMAN RETROVIRUS FROM WEST-AFRICAN PATIENTS WITH AIDS
    CLAVEL, F
    GUETARD, D
    BRUNVEZINET, F
    CHAMARET, S
    REY, MA
    SANTOSFERREIRA, MO
    LAURENT, AG
    DAUGUET, C
    KATLAMA, C
    ROUZIOUX, C
    KLATZMANN, D
    CHAMPALIMAUD, JL
    MONTAGNIER, L
    [J]. SCIENCE, 1986, 233 (4761) : 343 - 346
  • [5] SIGNAL TRANSDUCTION - IMMUNOSUPPRESSANTS AT WORK
    DEFRANCO, AL
    [J]. NATURE, 1991, 352 (6338) : 754 - 755
  • [6] DOURNON E, 1988, LANCET, V2, P1297
  • [7] ELLRODT A, 1984, LANCET, V1, P1383
  • [8] CYCLOSPORINE-A SPECIFICALLY INHIBITS FUNCTION OF NUCLEAR PROTEINS INVOLVED IN T-CELL ACTIVATION
    EMMEL, EA
    VERWEIJ, CL
    DURAND, DB
    HIGGINS, KM
    LACY, E
    CRABTREE, GR
    [J]. SCIENCE, 1989, 246 (4937) : 1617 - 1620
  • [9] NUCLEAR-ASSOCIATION OF A T-CELL TRANSCRIPTION FACTOR BLOCKED BY FK-506 AND CYCLOSPORINE-A
    FLANAGAN, WM
    CORTHESY, B
    BRAM, RJ
    CRABTREE, GR
    [J]. NATURE, 1991, 352 (6338) : 803 - 807
  • [10] PROTEIN FOLDING IN THE CELL
    GETHING, MJ
    SAMBROOK, J
    [J]. NATURE, 1992, 355 (6355) : 33 - 45