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Journal of Virology, October 2007, p. 11352-11362, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.01081-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Characterization of Human Immunodeficiency Virus Type 1 Replication in Immature and Mature Dendritic Cells Reveals Dissociable cis- and trans-Infection{triangledown}

Chunsheng Dong, Alicia M. Janas, Jian-Hua Wang, Wendy J. Olson,{dagger} and Li Wu*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226

Received 18 May 2007/ Accepted 26 July 2007

Dendritic cells (DCs) transmit human immunodeficiency virus type 1 (HIV-1) to CD4+ T cells through the trans- and cis-infection pathways; however, little is known about the relative efficiencies of these pathways and whether they are interdependent. Here we compare cis- and trans-infections of HIV-1 mediated by immature DCs (iDCs) and mature DCs (mDCs), using replication-competent and single-cycle HIV-1. Monocyte-derived iDCs were differentiated into various types of mDCs by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-{alpha}), and CD40 ligand (CD40L). iDCs and CD40L-induced mDCs were susceptible to HIV-1 infection and mediated efficient viral transmission to CD4+ T cells. Although HIV-1 cis-infection was partially restricted in TNF-{alpha}-induced mDCs and profoundly blocked in LPS-induced mDCs, these cells efficiently promoted HIV-1 trans-infection of CD4+ T cells. The postentry restriction of HIV-1 infection in LPS-induced mDCs was identified at the levels of reverse transcription and postintegration, using real-time PCR quantification of viral DNA and integration. Furthermore, nucleofection of DCs with HIV-1 proviral DNA confirmed that impaired gene expression of LPS-induced mDCs was responsible for the postentry restriction of HIV-1 infection. Our results suggest that various DC subsets in vivo may differentially contribute to HIV-1 dissemination via dissociable cis- and trans-infections.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. Phone: (414) 456-4075. Fax: (414) 456-6535. E-mail: liwu{at}mcw.edu

{triangledown} Published ahead of print on 8 August 2007.

{dagger} Present address: University of Wisconsin-Milwaukee, Milwaukee, WI 53201.

Journal of Virology, October 2007, p. 11352-11362, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.01081-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, J.-H., Kwas, C., Wu, L. (2009). Intercellular Adhesion Molecule 1 (ICAM-1), but Not ICAM-2 and -3, Is Important for Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission. J. Virol. 83: 4195-4204 [Abstract] [Full Text]  
  • Hatch, S. C., Archer, J., Gummuluru, S. (2009). Glycosphingolipid Composition of Human Immunodeficiency Virus Type 1 (HIV-1) Particles Is a Crucial Determinant for Dendritic Cell-Mediated HIV-1 trans-Infection. J. Virol. 83: 3496-3506 [Abstract] [Full Text]  
  • Dong, C., Kwas, C., Wu, L. (2009). Transcriptional Restriction of Human Immunodeficiency Virus Type 1 Gene Expression in Undifferentiated Primary Monocytes. J. Virol. 83: 3518-3527 [Abstract] [Full Text]  
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