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Mode of antiviral action of silver nanoparticles against HIV-1.

Lara HH, Ayala-Nuñez NV, Ixtepan-Turrent L, Rodriguez-Padilla C - J Nanobiotechnology (2010)

Bottom Line: Our data suggest that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry.Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle.These properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Inmunología y Virología, Departamento de Microbiología e Inmunología, Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico.

ABSTRACT

Background: Silver nanoparticles have proven to exert antiviral activity against HIV-1 at non-cytotoxic concentrations, but the mechanism underlying their HIV-inhibitory activity has not been not fully elucidated. In this study, silver nanoparticles are evaluated to elucidate their mode of antiviral action against HIV-1 using a panel of different in vitro assays.

Results: Our data suggest that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry. Silver nanoparticles bind to gp120 in a manner that prevents CD4-dependent virion binding, fusion, and infectivity, acting as an effective virucidal agent against cell-free virus (laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) and cell-associated virus. Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle.

Conclusions: These properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.

No MeSH data available.


Related in: MedlinePlus

Time-of-addition experiment. HeLa-CD4-LTR-β-gal cells were infected with HIV- 1IIIB, and silver nanoparticles (1 mg/mL) and different antiretrovirals were added at different times post infection. Activity of silver nanoparticles was compared with (A) Fusion inhibitors (Tak-779, 2 μM), (B) RT inhibitors (AZT, 20 μM), (C) Protease inhibitors (Indinavir, 0.25 μM), and (D) Integrase inhibitors (118-D-24, 100 μM). Dashed lines indicate the moment when the activity of the silver nanoparticles and the antiretroviral differ. The assay was performed in triplicate; the data points represent the mean and the colored lines are nonlinear regression curves done with SigmaPlot 10.0 software.
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Figure 2: Time-of-addition experiment. HeLa-CD4-LTR-β-gal cells were infected with HIV- 1IIIB, and silver nanoparticles (1 mg/mL) and different antiretrovirals were added at different times post infection. Activity of silver nanoparticles was compared with (A) Fusion inhibitors (Tak-779, 2 μM), (B) RT inhibitors (AZT, 20 μM), (C) Protease inhibitors (Indinavir, 0.25 μM), and (D) Integrase inhibitors (118-D-24, 100 μM). Dashed lines indicate the moment when the activity of the silver nanoparticles and the antiretroviral differ. The assay was performed in triplicate; the data points represent the mean and the colored lines are nonlinear regression curves done with SigmaPlot 10.0 software.

Mentions: To further determine the antiviral target of silver nanoparticles, a time-of-addition experiment was performed using a single cycle infection assay. The time-of-addition experiment was used to delimit the stage(s) of the viral life cycle that is blocked by silver nanoparticles. HeLa cells (expressing CD4, CXCR4 and CCR5) were infected with HIV-1IIIB cell-free virus and either silver nanoparticles (1.0 mg/mL), Tak-779 (2.0 μM), AZT (20.0 μM), Indinavir (0.25 μM), or 118-D-24 (100.0 μM) was added upon HIV-1 inoculation (time zero) or at various time points post-inoculation. These antiretroviral drugs were chosen as controls as they point out different stages of the viral cycle (fusion or entry, retrotranscription, protease activity, and integration to the genome). As seen in Figure 2(A-D), the antiviral activity of Tak-779, AZT, Indinavir, and 118-D-24 started to decline after the cycle stage that they target has passed. The fusion inhibitor's activity declined after 2 h (Figure 2A), RT inhibitors after 4 h (Figure 2B), protease inhibitors after 7 h (Figure 2C), and integrase inhibitors after 12 h (Figure 2D). In contrast, silver nanoparticles retained their antiviral activity even when added 12 h after the HIV inoculation. These results show that silver nanoparticles intervene with the viral life cycle at stages besides fusion or entry. These post-entry stages cover a time period between and including viral entry and the integration into the host genome.


Mode of antiviral action of silver nanoparticles against HIV-1.

Lara HH, Ayala-Nuñez NV, Ixtepan-Turrent L, Rodriguez-Padilla C - J Nanobiotechnology (2010)

Time-of-addition experiment. HeLa-CD4-LTR-β-gal cells were infected with HIV- 1IIIB, and silver nanoparticles (1 mg/mL) and different antiretrovirals were added at different times post infection. Activity of silver nanoparticles was compared with (A) Fusion inhibitors (Tak-779, 2 μM), (B) RT inhibitors (AZT, 20 μM), (C) Protease inhibitors (Indinavir, 0.25 μM), and (D) Integrase inhibitors (118-D-24, 100 μM). Dashed lines indicate the moment when the activity of the silver nanoparticles and the antiretroviral differ. The assay was performed in triplicate; the data points represent the mean and the colored lines are nonlinear regression curves done with SigmaPlot 10.0 software.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2818642&req=5

Figure 2: Time-of-addition experiment. HeLa-CD4-LTR-β-gal cells were infected with HIV- 1IIIB, and silver nanoparticles (1 mg/mL) and different antiretrovirals were added at different times post infection. Activity of silver nanoparticles was compared with (A) Fusion inhibitors (Tak-779, 2 μM), (B) RT inhibitors (AZT, 20 μM), (C) Protease inhibitors (Indinavir, 0.25 μM), and (D) Integrase inhibitors (118-D-24, 100 μM). Dashed lines indicate the moment when the activity of the silver nanoparticles and the antiretroviral differ. The assay was performed in triplicate; the data points represent the mean and the colored lines are nonlinear regression curves done with SigmaPlot 10.0 software.
Mentions: To further determine the antiviral target of silver nanoparticles, a time-of-addition experiment was performed using a single cycle infection assay. The time-of-addition experiment was used to delimit the stage(s) of the viral life cycle that is blocked by silver nanoparticles. HeLa cells (expressing CD4, CXCR4 and CCR5) were infected with HIV-1IIIB cell-free virus and either silver nanoparticles (1.0 mg/mL), Tak-779 (2.0 μM), AZT (20.0 μM), Indinavir (0.25 μM), or 118-D-24 (100.0 μM) was added upon HIV-1 inoculation (time zero) or at various time points post-inoculation. These antiretroviral drugs were chosen as controls as they point out different stages of the viral cycle (fusion or entry, retrotranscription, protease activity, and integration to the genome). As seen in Figure 2(A-D), the antiviral activity of Tak-779, AZT, Indinavir, and 118-D-24 started to decline after the cycle stage that they target has passed. The fusion inhibitor's activity declined after 2 h (Figure 2A), RT inhibitors after 4 h (Figure 2B), protease inhibitors after 7 h (Figure 2C), and integrase inhibitors after 12 h (Figure 2D). In contrast, silver nanoparticles retained their antiviral activity even when added 12 h after the HIV inoculation. These results show that silver nanoparticles intervene with the viral life cycle at stages besides fusion or entry. These post-entry stages cover a time period between and including viral entry and the integration into the host genome.

Bottom Line: Our data suggest that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry.Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle.These properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Inmunología y Virología, Departamento de Microbiología e Inmunología, Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico.

ABSTRACT

Background: Silver nanoparticles have proven to exert antiviral activity against HIV-1 at non-cytotoxic concentrations, but the mechanism underlying their HIV-inhibitory activity has not been not fully elucidated. In this study, silver nanoparticles are evaluated to elucidate their mode of antiviral action against HIV-1 using a panel of different in vitro assays.

Results: Our data suggest that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry. Silver nanoparticles bind to gp120 in a manner that prevents CD4-dependent virion binding, fusion, and infectivity, acting as an effective virucidal agent against cell-free virus (laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) and cell-associated virus. Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle.

Conclusions: These properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.

No MeSH data available.


Related in: MedlinePlus