Li Wu, PhD
Assistant Professor
Microbiology and Molecular Genetics
Medical College of Wisconsin
Research Focus: HIV Interactions with Dendritic Cells
PhD: Shanghai Medical College, Fudan University (2000) Microbiology
Postdoctoral Training: National Cancer Institute, NIH
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Human immunodeficiency virus (HIV) infection is the leading killer worldwide among infectious diseases, incurring 2-3 million deaths annually. HIV has infected a total of more than 60 million people, over a third of whom have succumbed to AIDS. Defining the mechanisms of HIV transmission and understanding the role of host factors and immune cells that participate in the transmission process are essential in developing effective strategies to combat HIV infection. Our research focuses on the molecular mechanisms by which immune cells help disseminate HIV. These studies will facilitate the development of more effective interventions against HIV transmission, and potentially aid in development of novel HIV vaccine strategies.
Dendritic cells (DCs) perform an essential role in the induction and regulation of the adaptive immune response, but they also function as a potent immunological vanguard against pathogens that cross mucosal tissues. DCs are thought to be among the first cells to encounter HIV when it penetrates the mucosa. Significantly, co-culture of HIV-pulsed-DCs with CD4+ T cells, the primary target for HIV infection and replication, greatly enhances infection of the T cell compartment. A C-type lectin named DC-SIGN (DC-specific ICAM-3 grabbing nonintegrin) has been identified as a key mediator in transmission of HIV from DCs to CD4+ T cells. DC-SIGN efficiently promotes HIV infection in trans. Virus captured via DC-SIGN is directed to infectious synapses that form between DCs and CD4+ target cells. However, the mechanism through which captured HIV eludes destruction and traffics to cellular synaptic junctions is unclear. Interestingly, HIV also exploits DC-SIGN-independent capture and trafficking mechanisms to promote its transmission from DCs to the T cell compartment.
To better understand the viral transmission mechanism, we are using molecular biological, cellular, and immunological approaches to define HIV interactions with DCs at the molecular level. These studies have relevance to viral pathogenesis and the mucosal transmission of HIV. DC-SIGN has also been identified as an attachment factor for a number of other significant human pathogens. Thus, examination of DC-SIGN function in HIV infection may contribute to our understanding of DC-mediated dissemination of other infectious agents.
Dendritic cells (red) interact with HIV virus-like particles (VLPs, green) and transmit VLPs to human CD4+ T cells (blue).
Recent Publications
Janas AM, Wu L. HIV-1 interactions with cells: from viral binding to cell-cell transmission. Current Protocols in Cell Biology. 2008: in press.
Wu L. Biology of HIV mucosal transmission. Current Opinion in HIV and AIDS. 2008; 3 (5): in press.
Janas AM, Dong C, Wang JH, Wu L. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry. Virology. 2008 Jun 5;375(2):442-51. Epub 2008 Mar 10.
Abstract
Dong C, Janas AM, Wang JH, Olson WJ, and Wu L. Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis- and trans-infection. J Virol. 2007 Oct;81:(20) 11352-62. Epub 2007 Aug 8.
Abstract
Wang JH, Janas AM, Olson WJ, Wu L. Functionally distinct transmission of human immunodeficiency virus type 1 mediated by immature and mature dendritic cells. J Virol. 2007 Sep;81(17):8933-43. Epub 2007 Jun 13.
Abstract
Journal Cover Illustration
Wang JH, Janas AM, Olson WJ, KewalRamani VN, Wu L. CD4 coexpression regulates DC-SIGN-mediated transmission of human immunodeficiency virus type 1. J Virol. 2007 Mar;81(5):2497-507. Epub 2006 Dec 6.
Abstract
Wu L, KewalRamani VN. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol. 2006 Nov;6(11):859-68.
Abstract
Garcia-Pineres AJ, Hildesheim A, Trivett M, Williams M, Wu L, KewalRamani VN, Pinto LA. Role of DC-SIGN in the activation of dendritic cells by HPV-16 L1 virus-like particle vaccine. Eur J Immunol. 2006 Feb;36(2):437-45
Abstract
Wu L, Martin TD, Han YC, Breun SK, KewalRamani VN. Trans-dominant cellular inhibition of DC-SIGN-mediated HIV-1 transmission. Retrovirology. 2004 Jun 28;1(1):14.
Abstract
Wu L, Martin TD, Carrington M, KewalRamani VN. Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission. Virology. 2004 Jan 5;318(1):17-23.
Abstract
McDonald D, Wu L, Bohks SM, KewalRamani VN, Unutmaz D, Hope TJ. Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science. 2003 May 23;300(5623):1295-7. Epub 2003 May 1.
Abstract
Bashirova AA, Wu L, Cheng J, Martin TD, Martin MP, Benveniste RE, Lifson JD, KewalRamani VN, Hughes A, Carrington M. Novel member of the CD209 (DC-SIGN) gene family in primates. J Virol. 2003 Jan;77(1):217-27.
Abstract
Wu L, Martin TD, Vazeux R, Unutmaz D, KewalRamani VN. Functional evaluation of DC-SIGN monoclonal antibodies reveals DC-SIGN interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission. J Virol. 2002 Jun;76(12):5905-14.
Abstract
Wu L, Bashirova AA, Martin TD, Villamide L, Mehlhop E, Chertov AO, Unutmaz D, Pope M, Carrington M, KewalRamani VN. Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1568-73. Epub 2002 Jan 29.
Abstract
Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Eilering JB, Martin MP, Wu L, Martin TD, Viebig N, Knolle PA, KewalRamani VN, van Kooyk Y, Carrington M. A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med. 2001 Mar 19;193(6):671-8.
Abstract
Contact Information
Email: liwu@mcw.edu
Phone: 414-456-4075
Room: BSB-203