APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection

HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction...

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Main Authors:	Pion, Marjorie, Granelli-Piperno, Angela, Mangeat, Bastien, Stalder, Romaine, Correa, Rafael, Steinman, Ralph M., Piguet, Vincent
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118170/

id	pubmed-2118170
recordtype	oai_dc
spelling	pubmed-21181702007-12-13 APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection Pion, Marjorie Granelli-Piperno, Angela Mangeat, Bastien Stalder, Romaine Correa, Rafael Steinman, Ralph M. Piguet, Vincent Articles HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA–mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry. The Rockefeller University Press 2006-12-25 /pmc/articles/PMC2118170/ /pubmed/17145955 http://dx.doi.org/10.1084/jem.20061519 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Pion, Marjorie Granelli-Piperno, Angela Mangeat, Bastien Stalder, Romaine Correa, Rafael Steinman, Ralph M. Piguet, Vincent
spellingShingle	Pion, Marjorie Granelli-Piperno, Angela Mangeat, Bastien Stalder, Romaine Correa, Rafael Steinman, Ralph M. Piguet, Vincent APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection
author_facet	Pion, Marjorie Granelli-Piperno, Angela Mangeat, Bastien Stalder, Romaine Correa, Rafael Steinman, Ralph M. Piguet, Vincent
author_sort	Pion, Marjorie
title	APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection
title_short	APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection
title_full	APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection
title_fullStr	APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection
title_full_unstemmed	APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection
title_sort	apobec3g/3f mediates intrinsic resistance of monocyte-derived dendritic cells to hiv-1 infection
description	HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA–mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118170/
_version_	1611414601665085440

APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection

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