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J Virol ; 74(12): 5577-86, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10823865

ABSTRACT

Heterosexual transmission of human immunodeficiency virus (HIV) is the most frequent mode of infection worldwide. However, the immediate events between exposure to infectious virus and establishment of infection are still poorly understood. This study investigates parameters of HIV infection of human female genital tissue in vitro using an explant culture model. In particular, we investigated the role of the epithelium and virucidal agents in protection against HIV infection. We have demonstrated that the major target cells of infection reside below the genital epithelium, and thus HIV must cross this barrier to establish infection. Immune activation enhanced HIV infection of such subepithelial cells. Furthermore, our data suggest that genital epithelial cells were not susceptible to HIV infection, appear to play no part in the transfer of infectious virus across the epithelium, and thus may provide a barrier to infection. In addition, experiments using a panel of virucidal agents demonstrated differential efficiency to block HIV infection of subepithelial cells from partial to complete inhibition. This is the first demonstration that virucidal agents designed for topical vaginal use block HIV infection of genital tissue. Such agents have major implications for world health, as they will provide women with a mechanism of personal and covert protection from HIV infection.


Subject(s)
Antiviral Agents/pharmacology , Cervix Uteri/virology , HIV Infections/prevention & control , HIV Infections/transmission , HIV-1/drug effects , HIV-1/physiology , Cell Polarity , Cells, Cultured , Cervix Uteri/cytology , Cervix Uteri/drug effects , Cervix Uteri/ultrastructure , Culture Techniques , DNA, Viral/biosynthesis , DNA, Viral/genetics , Epithelial Cells/drug effects , Epithelial Cells/ultrastructure , Epithelial Cells/virology , Female , Gramicidin/pharmacology , HIV Infections/virology , HIV-1/genetics , HIV-1/ultrastructure , Humans , Immunohistochemistry , Lymphocyte Activation/drug effects , Microscopy, Electron , Mucous Membrane/cytology , Mucous Membrane/drug effects , Mucous Membrane/ultrastructure , Mucous Membrane/virology , Naphthalenesulfonates/pharmacology , Nonoxynol/pharmacology , Phytohemagglutinins/pharmacology , Polymers/pharmacology , Premenopause , Virus Replication/drug effects
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