Sugar-binding proteins potently inhibit dendritic cell human immunodeficiency virus type 1 (HIV-1) infection and dendritic-cell-directed HIV-1 transfer.
Both endocytic uptake and viral fusion can lead to human immunodeficiency virus type 1 (HIV-1) transfer to CD4+ lymphocytes, either through directional regurgitation (infectious transfer in trans [I-IT]) or through de novo viral production in dendritic cells (DCs) resulting in a second-phase transfer to CD4+ lymphocytes (infectious second-phase transfer [I-SPT]). We have evaluated in immature monocyte-derived DCs both pathways of transfer with regard to their susceptibilities to being blocked by potential microbicidal compounds, including cyanovirin (CNV); the plant lectins Hippeastrum hybrid agglutinin, Galanthus nivalis agglutinin, Urtica dioica agglutinin, and Cymbidium hybrid agglutinin; and the glycan mannan. I-IT was a relatively inefficient means of viral transfer compared to I-SPT at both high and low levels of the viral inoculum. CNV was able to completely block I-IT at 15 microg/ml. All other compounds except mannan could inhibit I-IT by at least 90% when used at doses of 15 microg/ml. In contrast, efficient inhibition of I-SPT was remarkably harder to achieve, as 50% effective concentration levels for plant lectins and CNV to suppress this mode of HIV-1 transfer increased significantly. Thus, our findings indicate that I-SPT may be more elusive to targeting by antiviral drugs and stress the need for drugs affecting the pronounced inhibition of the infection of DCs by HIV-1.
Turville
Stuart G
SG
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Vermeire
Kurt
K
Balzarini
Jan
J
Schols
Dominique
D
D001426:Bacterial Proteins / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002352:Carrier Proteins / Q000494:pharmacology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000821:virology; D004305:Dose-Response Relationship, Drug; D027801:Galanthus; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D019668:Liliaceae; D037121:Plant Lectins / Q000494:pharmacology*; D026982:Urtica dioica
D001426:Bacterial Proteins; D002352:Carrier Proteins; D037121:Plant Lectins; C107733:cyanovirin N