Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for antiviral activity

2006 ◽  
Vol 344 (3) ◽  
pp. 792-797 ◽  
Author(s):  
Monique R. Ferguson ◽  
Daniel R. Rojo ◽  
Anoma Somasunderam ◽  
Varatharasa Thiviyanathan ◽  
Bettye D. Ridley ◽  
...  
1994 ◽  
Vol 5 (1) ◽  
pp. 43-45 ◽  
Author(s):  
S. Galpin ◽  
N. A. Roberts ◽  
T. O'Connor ◽  
D. J. Jeffries ◽  
D. Kinchington

The peptide derivative Ro 31-8959 has been shown to be a potent inhibitor of HIV proteinase with an IC50 of 2 × 10−9M, against HIV-1RF in acutely infected lymphoblastoid cells. This inhibition was not overcome by increasing the infectious dose or by extending the culture time. Similar antiviral activity was also obtained against HIV-2, SIV and several AZT-resistant strains of HIV-1. The time of addition of the inhibitor could be delayed for 22 h without significant loss of activity, supporting its mode of action as taking place late in the replication cycle of HIV-1. Ro 31-8959 also showed activity against chronically infected cells.


1996 ◽  
Vol 31 (1-2) ◽  
pp. 59-67 ◽  
Author(s):  
Karl Y. Hostetler ◽  
Ganesh D. Kini ◽  
James R. Beadle ◽  
Kathy A. Aldern ◽  
Michael F. Gardner ◽  
...  

2014 ◽  
Vol 30 (S1) ◽  
pp. A177-A178
Author(s):  
Esther Jimenez ◽  
Henrik Kloverpis ◽  
Ruth Peña ◽  
Nuria Izquierdo-Useros ◽  
Clotet Bonaventura ◽  
...  

2004 ◽  
Vol 280 (4) ◽  
pp. 3029-3042 ◽  
Author(s):  
Emmanuel Agbottah ◽  
Cynthia de La Fuente ◽  
Sergie Nekhai ◽  
Anna Barnett ◽  
Athos Gianella-Borradori ◽  
...  

1995 ◽  
Vol 28 (2) ◽  
pp. 113-120 ◽  
Author(s):  
H XIE ◽  
M VORONKOV ◽  
D LIOTTA ◽  
B KORBA ◽  
R SCHINAZI ◽  
...  

2005 ◽  
Vol 86 (8) ◽  
pp. 2221-2229 ◽  
Author(s):  
Lucile Espert ◽  
Geneviève Degols ◽  
Yea-Lih Lin ◽  
Thierry Vincent ◽  
Monsef Benkirane ◽  
...  

Interferons (IFNs) encode a family of secreted proteins that provide the front-line defence against viral infections. It was recently shown that ISG20, a new 3′→5′ exoribonuclease member of the DEDD superfamily of exonucleases, represents a novel antiviral pathway in the mechanism of IFN action. In this report, it was shown that ISG20 expression is rapidly and strongly induced during human immunodeficiency virus type 1 (HIV-1) infection. In addition, it was demonstrated that the replication kinetics of an HIV-1-derived virus expressing the ISG20 protein (HIV-1NL4-3ISG20) was delayed in both CEM cells and peripheral blood mononuclear cells. No antiviral effect was observed in cells overexpressing a mutated ISG20 protein defective in exonuclease activity, suggesting that the antiviral effect was due to the exonuclease activity of ISG20. Paradoxically, despite the antiviral activity of ISG20 protein, virus rescue observed in HIV-1NL4-3ISG20-infected cells was not due to mutation or partial deletion of the ISG20 transgene, suggesting that the virus was able to counteract the cellular defences. In addition, HIV-1-induced apoptosis was significantly reduced in HIV-1NL4-3ISG20-infected cells suggesting that emergence of HIV-1NL4-3ISG20 was associated with the inhibition of HIV-1-induced apoptosis. Altogether, these data reflect the ineffectiveness of virus replication in cells overexpressing ISG20 and demonstrate that ISG20 represents a new factor in the IFN-mediated antiviral barrier against HIV-1.


2004 ◽  
Vol 78 (2) ◽  
pp. 561-567 ◽  
Author(s):  
Ayub Ali ◽  
Rachel Lubong ◽  
Hwee Ng ◽  
David G. Brooks ◽  
Jerome A. Zack ◽  
...  

ABSTRACT The determinants of CD8+ cytotoxic T-lymphocyte (CTL) antiviral activity against human immunodeficiency virus type 1 (HIV-1) remain poorly defined. Although recent technological advances have markedly enhanced the ability to detect HIV-1-specific T cells, commonly used assays do not reveal their direct interaction with virus. We investigated two determinants of CTL antiviral efficiency by manipulating HIV-1 and measuring the effects on CTL suppression of viral replication in acutely infected cells. Translocation of a Gag epitope into the early protein Nef markedly increased the activity of CTL recognizing that epitope, in comparison to HIV-1 expressing the epitope normally in the late protein Gag. Because this epitope translocation resulted not only in earlier expression but also in loss of major histocompatibility complex class I downregulation by Nef, the activities of CTL against a panel of viral constructs differing in kinetics of epitope expression and class I downmodulation were compared. The results indicated that both the timing of epitope expression and the reduction of class I have profound effects on the ability of CTL to suppress HIV-1 replication in acutely infected cells. The epitope targeting of CTL and viral control of class I therefore likely play important roles in the ability of CTL to exert pressure on HIV-1.


1998 ◽  
Vol 72 (8) ◽  
pp. 6851-6857 ◽  
Author(s):  
C. A. Van Baalen ◽  
M. Schutten ◽  
R. C. Huisman ◽  
P. H. M. Boers ◽  
R. A. Gruters ◽  
...  

ABSTRACT The antiviral activity of a CD8+ cytotoxic T-lymphocyte (CTL) clone (TCC108) directed against a newly identified HLA-B14-restricted epitope, human immunodeficiency virus type 1 (HIV-1) Rev(67-75) SAEPVPLQL, was analyzed with respect to its kinetics of target cell lysis and inhibition of HIV-1 production. Addition of TCC108 cells or CD8+ reverse transcriptase-specific CTLs to HLA-matched CD4+ T cells at different times after infection with HIV-1 IIIB showed that infected cells became susceptible to CTL-mediated lysis before peak virus production but after the onset of progeny virus release. When either of these CTLs were added to part of the infected cells immediately after infection, p55 expression and virus production were significantly suppressed. These data support a model in which CTLs, apart from exerting cytolytic activity which may prevent continued virus release, can interfere with viral protein expression during the eclipse phase via noncytolytic mechanisms. TCC108-mediated inhibition of virus replication in peripheral blood mononuclear cells caused rapid selection of a virus with a mutation (69E→K) in the Rev(67-75) CTL epitope which abolished recognition by TCC108 cells. Taken together, these data suggest that both cytolytic and noncytolytic antiviral mechanisms of CTLs can be specifically targeted to HIV-1-infected cells.


Author(s):  
Sheriah Laine Maasin de Paz-Silava ◽  
Ann Florence B. Victoriano-Belvis ◽  
Nina G. Gloriani ◽  
Yurina Hibi ◽  
Kaori Asamitsu ◽  
...  

1998 ◽  
Vol 9 (1) ◽  
pp. 33-40 ◽  
Author(s):  
JR Beadle ◽  
GD Kini ◽  
KA Aldern ◽  
MF Gardner ◽  
KN Wright ◽  
...  

In a previous study, we reported that 1- O-octadecyl- sn-glycero-3-foscarnet (ODG-PFA) was 40 to 93 times more potent than free foscarnet (PFA) in human cytomegalovirus (HCMV)-, herpes simplex virus type 1 (HSV-1)- and human immunodeficiency virus type 1 (HIV-1)-infected cells. To evaluate the effect of substituting a 1- S-alkyl thioether for a 1- O-alkyl ether, we synthesized a series of PFA conjugates of 1- S-alkyl- sn-thioglycerols with varied 1- S-alkyl chain lengths. To establish structure–activity relationships we measured the in vitro antiviral activity of liposomal formulations of the drugs in cells infected with HCMV, HSV-1 or HIV-1. The optimum 1- S-alkyl chain length in the series was 16 to 18 carbon atoms. We compared the antiviral activity of 16- and 18-carbon alkyl thioglycerol versus alkylglycerol prodrugs and did not observe any significant differences in their antiviral activities. The series' most active member, 1- S-octadecyl- sn-glycero-3-foscarnet (ODSG-PFA) was 56-, eight- and 45-fold more active than PFA in HCMV-, HSV-1- and HIV-1-infected cells in vitro. The oral absorption of PFA and 1-S-octadecyl-sn-thioglycero-3-PFA was compared in mice by measuring plasma levels of 14C after oral administration of radiolabelled compounds. The peak plasma level of 14C was sevenfold higher following administration of [14C]ODSG-PFA than following an equimolar dose of [14C]PFA. Area-under-the-curve was 23-fold greater for ODSG-PFA than for PFA. Like previously reported alkyloxyether–lipid PFA conjugates, alkylthioether conjugates provided enhanced antiviral activity and oral bioavailability. However, S-ether conjugates may be metabolized differently than O-ether conjugates. More detailed in vivo pharmacokinetic evaluation of the alkyl-thioether–PFA conjugates is required.


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