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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

Inhibition of the gp120-CD4 interaction. (A) A cell-based fusion assay was used to mimic the gp120-CD4 mediated fusion of the viral and host cell membranes. HL2/3 and HeLa-CD4-LTR-β-gal cells were incubated with a two-fold serial dilution of silver nanoparticles and known antiretrovirals. The assay was performed in triplicate; the data points represent the mean ± s.e.m. (B) The degree of inhibition of the gp120-CD4 protein binding was assessed with a gp120/CD4 ELISA capture in the presence or absence of silver nanoparticles. Gp120 protein was pretreated for 10 min with a two-fold serial dilution of silver nanoparticles, then added to a CD4-coated plate. The assay was done twice; the error bars indicate the s.e.m.
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Figure 1: Inhibition of the gp120-CD4 interaction. (A) A cell-based fusion assay was used to mimic the gp120-CD4 mediated fusion of the viral and host cell membranes. HL2/3 and HeLa-CD4-LTR-β-gal cells were incubated with a two-fold serial dilution of silver nanoparticles and known antiretrovirals. The assay was performed in triplicate; the data points represent the mean ± s.e.m. (B) The degree of inhibition of the gp120-CD4 protein binding was assessed with a gp120/CD4 ELISA capture in the presence or absence of silver nanoparticles. Gp120 protein was pretreated for 10 min with a two-fold serial dilution of silver nanoparticles, then added to a CD4-coated plate. The assay was done twice; the error bars indicate the s.e.m.

Mentions: A cell-based fusion assay was used to mimic the gp120-CD4-mediated fusion process of HIV-1 to the host cell. HL2/3 cells, which express HIV-1 Env on their surfaces and Tat protein in their cytoplasms (effector cells) [27] and HeLa-CD4-LTR-β-gal (indicator cells) can fuse as the result of the gp120-CD4 interaction, and the amount of fused cells can be measured with the β-gal reporter gene. In the presence of a HL2/3-HeLa CD4 mixture, silver nanoparticles efficiently blocked fusion between both cells (Figure 1A) in a dose-dependent manner (1.0-2.5 mg/mL range). This concentration range is close to what we previously reported for silver nanoparticles IC50. Known antiretroviral drugs used as controls, such as UC781 (NNRTI), AZT (NRTI), and Indinavir (PI), did not inhibit cell fusion in this cell-based fusion assay.


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

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

Inhibition of the gp120-CD4 interaction. (A) A cell-based fusion assay was used to mimic the gp120-CD4 mediated fusion of the viral and host cell membranes. HL2/3 and HeLa-CD4-LTR-β-gal cells were incubated with a two-fold serial dilution of silver nanoparticles and known antiretrovirals. The assay was performed in triplicate; the data points represent the mean ± s.e.m. (B) The degree of inhibition of the gp120-CD4 protein binding was assessed with a gp120/CD4 ELISA capture in the presence or absence of silver nanoparticles. Gp120 protein was pretreated for 10 min with a two-fold serial dilution of silver nanoparticles, then added to a CD4-coated plate. The assay was done twice; the error bars indicate the s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Inhibition of the gp120-CD4 interaction. (A) A cell-based fusion assay was used to mimic the gp120-CD4 mediated fusion of the viral and host cell membranes. HL2/3 and HeLa-CD4-LTR-β-gal cells were incubated with a two-fold serial dilution of silver nanoparticles and known antiretrovirals. The assay was performed in triplicate; the data points represent the mean ± s.e.m. (B) The degree of inhibition of the gp120-CD4 protein binding was assessed with a gp120/CD4 ELISA capture in the presence or absence of silver nanoparticles. Gp120 protein was pretreated for 10 min with a two-fold serial dilution of silver nanoparticles, then added to a CD4-coated plate. The assay was done twice; the error bars indicate the s.e.m.
Mentions: A cell-based fusion assay was used to mimic the gp120-CD4-mediated fusion process of HIV-1 to the host cell. HL2/3 cells, which express HIV-1 Env on their surfaces and Tat protein in their cytoplasms (effector cells) [27] and HeLa-CD4-LTR-β-gal (indicator cells) can fuse as the result of the gp120-CD4 interaction, and the amount of fused cells can be measured with the β-gal reporter gene. In the presence of a HL2/3-HeLa CD4 mixture, silver nanoparticles efficiently blocked fusion between both cells (Figure 1A) in a dose-dependent manner (1.0-2.5 mg/mL range). This concentration range is close to what we previously reported for silver nanoparticles IC50. Known antiretroviral drugs used as controls, such as UC781 (NNRTI), AZT (NRTI), and Indinavir (PI), did not inhibit cell fusion in this cell-based fusion assay.

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