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 ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Double Stranded Dna ◽  
Infected Cells ◽  
Hiv 1

Antiviral Properties of the HIV-1 Proteinase Inhibitor RO 31-8959

1994 ◽  
Vol 5 (1) ◽  
pp. 43-45 ◽  
Author(s):  
S. Galpin ◽  
N. A. Roberts ◽  
T. O'Connor ◽  
D. J. Jeffries ◽  
D. Kinchington
Keyword(s):  
Antiviral Activity ◽  
Proteinase Inhibitor ◽  
Potent Inhibitor ◽  
Significant Loss ◽  
Infectious Dose ◽  
Culture Time ◽  
Infected Cells ◽  
Resistant Strains ◽  
Peptide Derivative ◽  
Hiv 1

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.

Lipid prodrugs of phosphonoacids: greatly enhanced antiviral activity of 1-O-octadecyl-sn-glycero-3-phosphonoformate in HIV-1, HSV-1 and HCMV-infected cells, in vitro

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 ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Infected Cells ◽  
Hiv 1 ◽  
Hsv 1

TRIM5α Improves CD8+ T-cell Antiviral Activity and Synergize Intrinsic Restriction and Adaptive Immunity in HIV-1 Infected Cells

2014 ◽  
Vol 30 (S1) ◽  
pp. A177-A178
Author(s):  
Esther Jimenez ◽  
Henrik Kloverpis ◽  
Ruth Peña ◽  
Nuria Izquierdo-Useros ◽  
Clotet Bonaventura ◽  
...  
Keyword(s):  
T Cell ◽  
Antiviral Activity ◽  
Adaptive Immunity ◽  
Cd8 T Cell ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Antiviral Activity of CYC202 in HIV-1-infected Cells

2004 ◽  
Vol 280 (4) ◽  
pp. 3029-3042 ◽  
Author(s):  
Emmanuel Agbottah ◽  
Cynthia de La Fuente ◽  
Sergie Nekhai ◽  
Anna Barnett ◽  
Athos Gianella-Borradori ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Infected Cells ◽  
Hiv 1

Phosphatidyl-2′,3′-dideoxy-3′-thiacytidine: synthesis and antiviral activity in hepatitis B- and HIV-1-infected cells

1995 ◽  
Vol 28 (2) ◽  
pp. 113-120 ◽  
Author(s):  
H XIE ◽  
M VORONKOV ◽  
D LIOTTA ◽  
B KORBA ◽  
R SCHINAZI ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Antiviral Activity ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1

2005 ◽  
Vol 86 (8) ◽  
pp. 2221-2229 ◽  
Author(s):  
Lucile Espert ◽  
Geneviève Degols ◽  
Yea-Lih Lin ◽  
Thierry Vincent ◽  
Monsef Benkirane ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Immunodeficiency Virus Type ◽  
Antiviral Effect ◽  
Exonuclease Activity ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Induced Apoptosis ◽  
Hiv 1

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.

scholarly journals Impacts of Epitope Expression Kinetics and Class I Downregulation on the Antiviral Activity of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes

2004 ◽  
Vol 78 (2) ◽  
pp. 561-567 ◽  
Author(s):  
Ayub Ali ◽  
Rachel Lubong ◽  
Hwee Ng ◽  
David G. Brooks ◽  
Jerome A. Zack ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Class I ◽  
Early Protein ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

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.

In vitro antiviral activity of Mentha cordifolia plant extract in HIV-1 latently infected cells using an established human cell line

2021 ◽  
Author(s):  
Sheriah Laine Maasin de Paz-Silava ◽  
Ann Florence B. Victoriano-Belvis ◽  
Nina G. Gloriani ◽  
Yurina Hibi ◽  
Kaori Asamitsu ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Cell Line ◽  
Plant Extract ◽  
Human Cell ◽  
Human Cell Line ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

Alkylthioglycerol Prodrugs of Foscarnet: Synthesis, Oral Bioavailability and Structure–Activity Studies in Human Cytomegalovirus-, Herpes Simplex Virus Type 1- and Human Immunodeficiency Virus Type 1-Infected Cells

1998 ◽  
Vol 9 (1) ◽  
pp. 33-40 ◽  
Author(s):  
JR Beadle ◽  
GD Kini ◽  
KA Aldern ◽  
MF Gardner ◽  
KN Wright ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Virus Type ◽  
Structure Activity ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hiv 1 ◽  
Hsv 1

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.

scholarly journals Potent and Selective Inhibition of Tat-Dependent HIV-1 Replication in Chronically Infected Cells by a Novel Naphthalene Derivative JTK-101

2007 ◽  
Vol 18 (4) ◽  
pp. 201-211 ◽  
Author(s):  
Xin Wang ◽  
Kazunobu Yamataka ◽  
Mika Okamoto ◽  
Satoru Ikeda ◽  
Masanori Baba
Keyword(s):  
Gene Expression ◽  
Antiviral Activity ◽  
Reporter Gene ◽  
Immunoblot Analysis ◽  
Reporter Gene Expression ◽  
Naphthalene Derivative ◽  
Cyclin T1 ◽  
Tnf Α ◽  
Infected Cells ◽  
Hiv 1

In search for effective human immunodeficiency virus type 1 (HIV-1) transcription inhibitors, we have evaluated more than 100,000 compounds for their inhibitory effects on HIV-1 long terminal repeat (LTR)-driven reporter gene expression, and identified a novel naphthalene derivative, JTK-101. This compound could suppress tumour necrosis factor (TNF)-α-induced HIV-1 production in latently infected OM-10.1 cells at nanomolar concentrations. JTK-101 could also potently inhibit constitutive HIV-1 production in MOTL-4/IIIB. However, the antiviral activity of JTK-101 was found to be much weaker in acutely infected cells and the chronically infected cells U937/IIIB cells than in OM-10.1 and MOLT-4/IIIB cells. JTK-101 selectively suppressed TNF-α-induced HIV-1 mRNA synthesis in OM-10.1 cells in a dose-dependent fashion. JTK-101 modestly inhibited TNF-α-induced HIV-1 LTR-driven reporter gene expression, but potently inhibited Tat-induced gene expression. Immunoblot analysis revealed that low-level expression of the Tat cofactors CDK9 and cyclin T1 might contribute to the diminished antiviral activity in U937/IIIB cells. Furthermore, JTK-101 could not inhibit HIV-1 replication in chronically infected monocytes/macrophages, in which CDK9 and cyclin T1 were undetectable. These results suggest that JTK-101 exerts its anti-HIV-1 activity through the inhibition of known or unknown Tat cofactors, presumably CDK9/cyclin T1.

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