Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.

Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory ef...

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Autores principales:	Angela Wahl, Michael D Swanson, Tomonori Nochi, Rikke Olesen, Paul W Denton, Morgan Chateau, J Victor Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b32c412acbeb41efab64fcd4be817126
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spelling	oai:doaj.org-article:b32c412acbeb41efab64fcd4be8171262021-11-18T06:04:18ZHuman breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.1553-73661553-737410.1371/journal.ppat.1002732https://doaj.org/article/b32c412acbeb41efab64fcd4be8171262012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22737068/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory effect has never been demonstrated in vivo. Here, we address this important paradox using the first humanized mouse model of oral HIV transmission. We established that reconstitution of the oral cavity and upper gastrointestinal (GI) tract of humanized bone marrow/liver/thymus (BLT) mice with human leukocytes, including the human cell types important for mucosal HIV transmission (i.e. dendritic cells, macrophages and CD4⁺ T cells), renders them susceptible to oral transmission of cell-free and cell-associated HIV. Oral transmission of HIV resulted in systemic infection of lymphoid and non-lymphoid tissues that is characterized by the presence of HIV RNA in plasma and a gradual decline of CD4⁺ T cells in peripheral blood. Consistent with infection of the oral cavity, we observed virus shedding into saliva. We then evaluated the role of human breast milk on oral HIV transmission. Our in vivo results demonstrate that breast milk has a strong inhibitory effect on oral transmission of both cell-free and cell-associated HIV. Finally, we evaluated the effect of antiretrovirals on oral transmission of HIV. Our results show that systemic antiretrovirals administered prior to exposure can efficiently prevent oral HIV transmission in BLT mice.Angela WahlMichael D SwansonTomonori NochiRikke OlesenPaul W DentonMorgan ChateauJ Victor GarciaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002732 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Angela Wahl Michael D Swanson Tomonori Nochi Rikke Olesen Paul W Denton Morgan Chateau J Victor Garcia Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.
description	Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory effect has never been demonstrated in vivo. Here, we address this important paradox using the first humanized mouse model of oral HIV transmission. We established that reconstitution of the oral cavity and upper gastrointestinal (GI) tract of humanized bone marrow/liver/thymus (BLT) mice with human leukocytes, including the human cell types important for mucosal HIV transmission (i.e. dendritic cells, macrophages and CD4⁺ T cells), renders them susceptible to oral transmission of cell-free and cell-associated HIV. Oral transmission of HIV resulted in systemic infection of lymphoid and non-lymphoid tissues that is characterized by the presence of HIV RNA in plasma and a gradual decline of CD4⁺ T cells in peripheral blood. Consistent with infection of the oral cavity, we observed virus shedding into saliva. We then evaluated the role of human breast milk on oral HIV transmission. Our in vivo results demonstrate that breast milk has a strong inhibitory effect on oral transmission of both cell-free and cell-associated HIV. Finally, we evaluated the effect of antiretrovirals on oral transmission of HIV. Our results show that systemic antiretrovirals administered prior to exposure can efficiently prevent oral HIV transmission in BLT mice.
format	article
author	Angela Wahl Michael D Swanson Tomonori Nochi Rikke Olesen Paul W Denton Morgan Chateau J Victor Garcia
author_facet	Angela Wahl Michael D Swanson Tomonori Nochi Rikke Olesen Paul W Denton Morgan Chateau J Victor Garcia
author_sort	Angela Wahl
title	Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.
title_short	Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.
title_full	Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.
title_fullStr	Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.
title_full_unstemmed	Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.
title_sort	human breast milk and antiretrovirals dramatically reduce oral hiv-1 transmission in blt humanized mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b32c412acbeb41efab64fcd4be817126
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Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.

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