Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

Background: Bovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- B)...

Descripción completa

Detalles Bibliográficos
Autores principales: Lara Villegas, Humberto Herman, Ixtepan Turrent, Liliana del Carmen, Garza Treviño, Elsa Nancy, Badillo Almaraz, José Isaías, Rodríguez Padilla, Cristina
Formato: Artículo
Lenguaje:inglés
Publicado: 2011
Materias:
Acceso en línea:http://eprints.uanl.mx/15056/1/674.pdf
_version_ 1824414241043513344
author Lara Villegas, Humberto Herman
Ixtepan Turrent, Liliana del Carmen
Garza Treviño, Elsa Nancy
Badillo Almaraz, José Isaías
Rodríguez Padilla, Cristina
author_facet Lara Villegas, Humberto Herman
Ixtepan Turrent, Liliana del Carmen
Garza Treviño, Elsa Nancy
Badillo Almaraz, José Isaías
Rodríguez Padilla, Cristina
author_sort Lara Villegas, Humberto Herman
collection Repositorio Institucional
description Background: Bovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- B) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays. Results: The cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action. HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-b-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours. Conclusions: bDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours. bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals.
format Article
id eprints-15056
institution UANL
language English
publishDate 2011
record_format eprints
spelling eprints-150562019-05-07T20:46:07Z http://eprints.uanl.mx/15056/ Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection Lara Villegas, Humberto Herman Ixtepan Turrent, Liliana del Carmen Garza Treviño, Elsa Nancy Badillo Almaraz, José Isaías Rodríguez Padilla, Cristina QR Microbiología RA Aspectos Públicos de la Medicina Background: Bovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- B) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays. Results: The cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action. HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-b-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours. Conclusions: bDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours. bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals. 2011 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/15056/1/674.pdf http://eprints.uanl.mx/15056/1.haspreviewThumbnailVersion/674.pdf Lara Villegas, Humberto Herman y Ixtepan Turrent, Liliana del Carmen y Garza Treviño, Elsa Nancy y Badillo Almaraz, José Isaías y Rodríguez Padilla, Cristina (2011) Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection. BMC Research Notes, 4 (1). p. 474. ISSN 1756-0500 http://doi.org/10.1186/1756-0500-4-474 doi:10.1186/1756-0500-4-474
spellingShingle QR Microbiología
RA Aspectos Públicos de la Medicina
Lara Villegas, Humberto Herman
Ixtepan Turrent, Liliana del Carmen
Garza Treviño, Elsa Nancy
Badillo Almaraz, José Isaías
Rodríguez Padilla, Cristina
Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
title_full Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
title_fullStr Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
title_full_unstemmed Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
title_short Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
title_sort antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection
topic QR Microbiología
RA Aspectos Públicos de la Medicina
url http://eprints.uanl.mx/15056/1/674.pdf
work_keys_str_mv AT laravillegashumbertoherman antiviralmodeofactionofbovinedialyzableleukocyteextractagainsthumanimmunodeficiencyvirustype1infection
AT ixtepanturrentlilianadelcarmen antiviralmodeofactionofbovinedialyzableleukocyteextractagainsthumanimmunodeficiencyvirustype1infection
AT garzatrevinoelsanancy antiviralmodeofactionofbovinedialyzableleukocyteextractagainsthumanimmunodeficiencyvirustype1infection
AT badilloalmarazjoseisaias antiviralmodeofactionofbovinedialyzableleukocyteextractagainsthumanimmunodeficiencyvirustype1infection
AT rodriguezpadillacristina antiviralmodeofactionofbovinedialyzableleukocyteextractagainsthumanimmunodeficiencyvirustype1infection