Functionally distinct transmission of human immunodeficiency virus type 1 mediated by immature and mature dendritic cells.

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Journal of Virology (Impact Factor: 4.65). 10/2007; 81(17):8933-43. DOI: 10.1128/JVI.00878-07
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Semen deposition results in modulated immunity and an inflammatory response of the genital mucosa, which promotes conditions facilitating conception and pregnancy. These semen-induced alterations in the female reproductive tract can also have implications for the sexual transmission of viral infections such as HIV-1. Semen is not only a vector for HIV-1 but also a carrier for pro- and antiviral factors. Semen induces significant mucosal changes upregulating gene, and transcription factors leading to recruitment and activation of HIV target cells, stimulation of HIV replication and potentiation of Toll-like receptor responses. Although more research is needed to clearly elucidate the resulting collective effects of all these factors, semen modulation of the cervicovaginal microenvironment and immune system appears to lead, through multiple mechanisms, to mucosal changes facilitating viral entry and replication, likely resulting in enhanced susceptibility to acquire HIV-1 infection.
    American Journal Of Reproductive Immunology 04/2014; · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The vast majority of new HIV infections in male-to-female transmission occurs through semen, where HIV-1 is present in two different forms: as free and as cell-associated virus. In the female lower genital tract, semen mixes with female genital secretions that contain various factors, some of which facilitate or inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches the regional lymph nodes, and disseminates through the female host. Cervico-vaginal mucosa contains multiple barriers, resulting in a low probability of vaginal transmission. However, in some cases, HIV-1 is able to break these barriers. Although the exact mechanisms of how these barriers function remain unclear, their levels of efficiency against cell-free and cell-associated HIV-1 are different, and both cell-free and cell-associated virions seem to use different strategies to overcome these barriers. Understanding the basic mechanisms of HIV-1 vaginal transmission is required for the development of new antiviral strategies to contain HIV-1 epidemics.
    American Journal Of Reproductive Immunology 04/2014; · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Persistent infections with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are a major cause of morbidity and mortality worldwide. As sentinels of our immune system, dendritic cells (DCs) play a central role in initiating and regulating a potent antiviral immune response. Recent advances in our understanding of the role of DCs during HIV-1 and HCV infection have provided crucial insights into the mechanisms employed by these viruses to impair DC functions in order to evade an effective immune response against them. Modulation of the immunological synapse between DC and T-cell, as well as dysregulation of the crosstalk between DCs and natural killer (NK) cells, are emerging as two crucial mechanisms. This review focuses on understanding the interaction of HIV-1 and HCV with DCs not only to understand the immunopathogenesis of chronic HIV-1 and HCV infection, but also to explore the possibilities of DC-based immunotherapeutic approaches against them. Host genetic makeup is known to play major roles in infection outcome and rate of disease progression, as well as response to anti-viral therapy in both HIV-1 and HCV-infected individuals. Therefore, we highlight the genetic variations that can potentially affect DC functions, especially in the setting of chronic viral infection. Altogether, we address if DCs' potential as critical effectors of antiviral immune response could indeed be utilized to combat chronic infection with HIV-1 and HCV.
    Virology: Research and Treatment 01/2013; 4:1-25.


1 Download
Available from