HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis

被引:17
作者
Barat, Corinne
Zhao, Chenqi
Ouellette, Marc
Tremblay, Michel J.
机构
[1] CHU Laval, Res Ctr Infect Dis, Lab Human Immunoretrovirol, Quebec City, PQ G1V 4G2, Canada
[2] Univ Laval, Fac Med, Laval, PQ, Canada
基金
加拿大健康研究院;
关键词
D O I
10.1086/510398
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium stibogluconate is a drug of choice for the treatment of leishmaniasis. Because sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV-1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory-adapted and clinical strains of HIV-1, we report that sodium stibogluconate induces an increase in HIV-1 transcription and virus replication in primary CD4(+) T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor-kappa B and activator protein 1, as well as the Syk, Jun, and mitogen-activated protein kinase/extracellular signal-related kinase signal-transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV-1-infected patients.
引用
收藏
页码:236 / 245
页数:10
相关论文
共 36 条
[1]  
ALJASER M, 1995, PHARM RES-DORDR, V12, P113, DOI 10.1023/A:1016251023427
[2]   Engagement of CD43 enhances human immunodeficiency virus type 1 transcriptional activity and virus production that is induced upon TCR/CD3 stimulation [J].
Barat, C ;
Tremblay, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (32) :28714-28724
[3]   Activation of HIV-1 long terminal repeat transcription and virus replication via NF-kappa B-dependent and -independent pathways by potent phosphotyrosine phosphatase inhibitors, the peroxovanadium compounds [J].
Barbeau, B ;
Bernier, R ;
Dumais, N ;
Briand, G ;
Olivier, M ;
Faure, R ;
Posner, BI ;
Tremblay, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (20) :12968-12977
[4]  
Basu JM, 2006, ANTIMICROB AGENTS CH, V50, P1788, DOI [10.1128/AAC.50.5.1768-1797.2006, 10.1128/AAC.50.5.1788-1797.2006]
[5]   HIV viral load and response to antileishmanial chemotherapy in co-infected patients [J].
Berhe, N ;
Wolday, D ;
Hailu, A ;
Abraham, Y ;
Ali, A ;
Gebre-Michael, T ;
Desjeux, P ;
Sönnerborg, A ;
Akuffo, H ;
Britton, S .
AIDS, 1999, 13 (14) :1921-1925
[6]   Human leishmaniasis: Clinical, diagnostic, and chemotherapeutic developments in the last 10 years [J].
Berman, JD .
CLINICAL INFECTIOUS DISEASES, 1997, 24 (04) :684-703
[7]   Presence of host ICAM-1 in laboratory and clinical strains of human immunodeficiency virus type 1 increases virus infectivity and CD4+-T-cell depletion in human lymphoid tissue, a major site of replication in vivo [J].
Bounou, S ;
Leclerc, JE ;
Tremblay, MJ .
JOURNAL OF VIROLOGY, 2002, 76 (03) :1004-1014
[8]   Prolonged Th-2 cell activation and increased viral replication in HIV-Leishmania co-infected patients despite treatment [J].
Cacopardo, B ;
Nigro, L ;
Preiser, W ;
Fama, A ;
Satariano, MI ;
Braner, J ;
Celesia, BM ;
Weber, B ;
Russo, R ;
Doerr, HW .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1996, 90 (04) :434-435
[9]  
Castellanos MD, 1997, J IMMUNOL, V159, P5463
[10]   PHARMACOKINETICS OF ANTIMONY DURING TREATMENT OF VISCERAL LEISHMANIASIS WITH SODIUM STIBOGLUCONATE OR MEGLUMINE ANTIMONIATE [J].
CHULAY, JD ;
FLECKENSTEIN, L ;
SMITH, DH .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1988, 82 (01) :69-72