Article

HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer.

Entrée Muqueuse du VIH et Immunité muqueuse, Departement de Biologie Cellulaire, Institut Cochin, CNRS, INSERM, Université René Descartes, 75014 Paris, France.
Molecular Biology of the Cell (Impact Factor: 4.55). 10/2005; 16(9):4267-79. DOI: 10.1091/mbc.E05-03-0192
Source: PubMed

ABSTRACT The heparan sulfate proteoglycan agrin and adhesion molecules are key players in the formation of neuronal and immune synapses that evolved for efficient communication at the sites of cell-cell contact. Transcytosis of infectious virus across epithelial cells upon contact between HIV-1-infected cells and the mucosal pole of the epithelial cells is one mechanism for HIV-1 entry at mucosal sites. In contrast, transcytosis of cell-free HIV-1 is not efficient. A synapse between HIV-1-infected cells and the mucosal epithelial surface that resembles neuronal and immune synapses is visualized by electron microscopy. We have termed this the "viral synapse." Similarities of the viral synapse also extend to the functional level. HIV-1-infected cell-induced transcytosis depends on RGD-dependent integrins and efficient cell-free virus transcytosis is inducible upon RGD-dependent integrin cross-linking. Agrin appears differentially expressed at the apical epithelial surface and acts as an HIV-1 attachment receptor. Envelope glycoprotein subunit gp41 binds specifically to agrin, reinforcing the interaction of gp41 to its epithelial receptor galactosyl ceramide.

0 Followers
 · 
60 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) continues to contribute to the global burden of disease despite great advances in antiretroviral (ARV) treatment and prophylaxis. In this review, we discuss the proposed mechanisms of MTCT, evidence for cell-free and cell-associated transmission in different routes of MTCT, and the impact of ARVs on virus levels and transmission. Many population-based studies support a role for cell-associated virus in transmission and in vitro studies also provide some support for this mode of transmission. However, animal model studies provide proof-of-principle that cell-free virus can establish infection in infants, and studies of ARVs in HIV-infected pregnant women show a strong correlation with reduction in cell-free virus levels and protection. ARV treatment in MTCT potentially provides opportunities to better define the infectious form of virus, but these studies will require better tools to measure the infectious cell reservoir. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    The Journal of Infectious Diseases 12/2014; 210(suppl 3):S631-S640. DOI:10.1093/infdis/jiu344 · 5.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) can efficiently spread by direct cell-to-cell contact, a mechanism termed cell-associated HIV transmission. By some estimates, cell-associated HIV transmission is 10-1000-fold more effective than cell-free HIV infection. Mucosal cell-associated HIV transmission may occur when HIV-bearing cells in mucosal secretions from an HIV-infected donor transfer virus directly to recipient target cells in or below the mucosal epithelium, or through HIV transcytosis across the mucosal epithelium of a noninfected host. This mechanism may play an important role in the sexual and vertical transmission of HIV-1, yet most in vitro tests of vaccine and microbicide efficacy assess cell-free virus transmission. This article reviews in vitro assays that have been used to model mucosal cell-associated transmission, including microscopy, immune cell cocultures, use of HIV-infected cells in epithelial cell transcytosis assays, and cell-associated infection of mucosal tissue explants. Assays that authentically simulate mucosal cell-associated HIV transmission could provide valuable insight into mechanisms and molecules that can potentially be targeted for HIV prevention, as well as critical models for testing novel HIV prevention strategies for efficacy against cell-associated HIV transmission. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    The Journal of Infectious Diseases 12/2014; 210(suppl 3):S648-S653. DOI:10.1093/infdis/jiu537 · 5.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs.
    BioMed Research International 01/2014; 2014:20. DOI:10.1155/2014/350195 · 2.71 Impact Factor

Preview

Download
0 Downloads
Available from