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Journal of Virology, September 2007, p. 8933-8943, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00878-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Functionally Distinct Transmission of Human Immunodeficiency Virus Type 1 Mediated by Immature and Mature Dendritic Cells{triangledown}

Jian-Hua Wang, Alicia M. Janas, 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 24 April 2007/ Accepted 3 June 2007

Dendritic cells (DCs) potently stimulate the transmission of human immunodeficiency virus type 1 (HIV-1) to CD4+ T cells. Immature DCs (iDCs) located in submucosal tissues can capture HIV-1 and migrate to lymphoid tissues, where they become mature DCs (mDCs) for effective antigen presentation. DC maturation promotes HIV-1 transmission; however, the underlying mechanisms remain unclear. Here we have compared monocyte-derived iDCs and mDCs for their efficiencies and mechanisms of HIV-1 transmission. We have found that mDCs significantly facilitate HIV-1 endocytosis and efficiently concentrate HIV-1 at virological synapses, which contributes to mDC-enhanced viral transmission, at least in part. mDCs were more efficient than iDCs in transferring HIV-1 to various types of target cells independently of C-type lectins, which partially accounted for iDC-mediated HIV-1 transmission. Efficient HIV-1 trans-infection mediated by iDCs and mDCs required contact between DCs and target cells. Moreover, rapid HIV-1 degradation occurred in both iDCs and mDCs, which correlated with the lack of HIV-1 retention-mediated long-term viral transmission. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission, suggesting that HIV-1 exploits mDCs to facilitate its dissemination within lymphoid tissues.


* 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 13 June 2007.

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


Journal of Virology, September 2007, p. 8933-8943, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00878-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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