Journal article
CD4 Coexpression Regulates DC-SIGN-Mediated Transmission of Human Immunodeficiency Virus Type 1
Journal of virology, Vol.81(5), pp.2497-2507
03/2007
DOI: 10.1128/JVI.01970-06
PMCID: PMC1865928
PMID: 17151103
Abstract
Dendritic cells (DCs) potently stimulate the cell-cell transmission of human immunodeficiency virus type 1 (HIV-1). However, the mechanisms that underlie DC transmission of HIV-1 to CD4
+
T cells are not fully understood. DC-SIGN, a C-type lectin, efficiently promotes HIV-1
trans
infection. DC-SIGN is expressed in monocyte-derived DCs (MDDCs), macrophage subsets, activated B lymphocytes, and various mucosal tissues. MDDC-mediated HIV-1 transmission to CD4
+
T cells involves DC-SIGN-dependent and -independent mechanisms. DC-SIGN transmission of HIV-1 depends on the donor cell type. HIV-1 Nef can upregulate DC-SIGN expression and promote DC-T-cell clustering and HIV-1 spread. Nef also downregulates CD4 expression; however, the effect of the CD4 downmodulation on DC-mediated HIV-1 transmission has not been examined. Here, we report that CD4 expression levels correlate with inefficient HIV-1 transmission by monocytic cells expressing DC-SIGN. Expression of CD4 on Raji B cells strongly impaired DC-SIGN-mediated HIV-1 transmission to T cells. By contrast, enhanced HIV-1 transmission was observed when CD4 molecules on MDDCs and DC-SIGN-CD4-expressing cell lines were blocked with specific antibodies. Coexpression of CD4 and DC-SIGN in Raji cells promoted the internalization and intracellular retention of HIV-1. Interestingly, internalized HIV-1 particles were sorted and confined to late endosomal compartments that were positive for CD63 and CD81. Furthermore, in HIV-1-infected MDDCs, significant downregulation of CD4 by Nef expression correlated with enhanced viral transmission. These results suggest that CD4, which is present at various levels in DC-SIGN-positive primary cells, is a key regulator of HIV-1 transmission.
Details
- Title: Subtitle
- CD4 Coexpression Regulates DC-SIGN-Mediated Transmission of Human Immunodeficiency Virus Type 1
- Creators
- Jian-Hua Wang - HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702Alicia M Janas - HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702Wendy J Olson - HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702Vineet N KewalRamani - HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702Li Wu - HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.81(5), pp.2497-2507
- DOI
- 10.1128/JVI.01970-06
- PMID
- 17151103
- PMCID
- PMC1865928
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 03/2007
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001107902771
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